Adherens junctions play pivotal roles in cell and tissue organization and patterning by mediating cell adhesion and cell signaling. These junctions consist of large multiprotein complexes that join the actin cytoskeleton to the plasma membrane to form adhesive contacts between cells or between cells and extracellular matrix. The best-known adherens junction is the zonula adherens (ZA) that forms a belt surrounding the apical pole of epithelial cells. Recent studies in Drosophila have further illuminated the structure (...) of adherens junctions. Scaffolding proteins encoded by the stardust gene are novel components of the Crumbs complex, which plays a critical role in ZA assembly.1-3 The small GTPase Rap1 controls the symmetric re-assembly of the ZA after cell division.4 Finally, the asymmetric distribution of adherens junction material regulates spindle orientation during asymmetric cell division in the sensory organ lineage.5 BioEssays 24:690–695, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

The integrity of epithelia depends largely on specialised adhesive structures, the adherens junctions. Several of the components required for building these structures are highly conserved between vertebrates and insects (e.g. E‐cadherin and α‐ and β‐catenin), while others have so far been found only in invertebrates (e.g. crumbs). Two recent papers(1,2) show that the Drosophila E‐cadherin is encoded by the gene shotgun. Phenotypic analyses of shotgun as well as armadillo (β‐catenin) and crumbs mutants provide new insights into the mechanisms (...) by which adherens junctions are built and, further, show that the requirement for E‐cadherin largely depends on the morphogenetic activity of an epithelium. (shrink)

There are many morphologically distinct membrane structures with different functions at the surface of epithelial cells. Among these, adherens junctions (AJ) and tight junctions (TJ) are responsible for the mechanical linkage of epithelial cells and epithelial barrier function, respectively. In the process of new cell–cell adhesion formation between two epithelial cells, such as after wounding, AJ form first and then TJ form on the apical side of AJ. This process is very complicated because AJ formation triggers drastic (...) changes in the organization of actin cytoskeleton, the activity of Rho family of small GTPases, and the lipid composition of the plasma membrane, all of which are required for subsequent TJ formation. In this review, the authors focus on the relationship between AJ and TJ as a representative example of specialization of plasma membrane regions and introduce recent findings on how AJ formation promotes the subsequent formation of TJ. (shrink)

Adherens (AJ) and tight junctions (TJ) maintain cell‐cell adhesions and cellular polarity in normal tissues. Afadin, a multi‐domain scaffold protein, is commonly found in both adherens and tight junctions, where it plays both structural and signal‐modulating roles. Afadin is a complex modulator of cellular processes implicated in cancer progression, including signal transduction, migration, invasion, and apoptosis. In keeping with the complexities associated with the roles of adherens and tight junctions in cancer, afadin exhibits both (...) tumor suppressive and pro‐metastatic functions. In this review, we will explore the dichotomous roles that afadin plays during cancer progression. (shrink)

Physical forces regulate numerous biological processes during development, physiology, and pathology. Forces between the external environment and intracellular actin cytoskeleton are primarily transmitted through integrin‐containing focal adhesions and cadherin‐containing adherens junctions. Crosstalk between these complexes is well established and modulates the mechanical landscape of the cell. However, integrins and cadherins constitute large families of adhesion receptors and form multiple complexes by interacting with different ligands, adaptor proteins, and cytoskeletal filaments. Recent findings indicate that integrin‐containing hemidesmosomes oppose force transduction (...) and traction force generation by focal adhesions. The cytolinker plectin mediates this crosstalk by coupling intermediate filaments to the actin cytoskeleton. Similarly, cadherins in desmosomes might modulate force generation by adherens junctions. Moreover, mechanotransduction can be influenced by podosomes, clathrin lattices, and tetraspanin‐enriched microdomains. This review discusses mechanotransduction by multiple integrin‐ and cadherin‐based cell adhesion complexes, which together with the associated cytoskeleton form an integrated network that allows cells to sense, process, and respond to their physical environment. (shrink)

MUC1 and MUC4 are the two membrane mucins that have been best characterized. Although they have superficially similar structures and have both been shown to provide steric protection of epithelial surfaces, recent studies have also implicated them in cellular signaling. They act by substantially different mechanisms, MUC4 as a receptor ligand and MUC1 as a docking protein for signaling molecules. MUC4 is a novel intramembrane ligand for the receptor tyrosine kinase ErbB2/HER2/Neu, triggering a specific phosphorylation of the ErbB2 in the (...) absence of other ErbB ligands and potentiating phosphorylation and signaling through the ErbB2/ErbB3 heterodimeric receptor complex formed in the presence of neuregulin. In contrast, MUC1 has a highly conserved cytoplasmic tail, which binds β‐catenin, a key component of adherens junctions and a regulator of transcription, in a process that is tightly regulated by MUC1 phosphorylation. The specific localization of these membrane mucins to the apical surfaces of epithelial cells suggests that their signaling functions may be important as sensor mechanisms in response to invasion or damage of epithelia. BioEssays 25:66–71, 2003. © 2002 Wiley Periodicals, Inc. (shrink)

Epithelial development dictates the shape of an organism. The metamorphic development of a Drosophila leg precursor into an adult leg is a well‐defined example of epithelial morphogenesis that can be analyzed from the perspectives of genetics and molecular and cell biology. The steroid hormone 20‐hydroxyecdysone induces and regulates the entire process. Mutants affecting Drosophila leg morphogenesis characteristically have short thick legs (the malformed phenotype) resulting from a failure to execute normal cell shape changes at a specific stage of development. Mutations (...) that cause the malformed phenotype have already led to the identification and cloning of genes encoding transcription factors, a transmembrane serine protease presumably required for modification of the apical extracellular matrix, and components of the contractile cytoskeleton and adherens junctions. All of these products are required for the execution of normal changes in leg cell shape. (shrink)

Several molecular mechanisms contribute directly and mechanically to the loss of epithelial phenotype. During epithelial–mesenchymal transition (EMT), adherens junctions and desmosomes are at least partially dissociated. At the same time, a massive cytoskeleton reorganization takes place, involving the rho family and the remodeling of the actin microfilament mesh. Numerous pathways have been described in vitro that control phenotype transition in specific cell models. In vivo developmental studies suggest that transcriptional control, activated by a specific pathway involving Ras, Src (...) and potentially the Wnt pathway, is an essential step. Recent functional and localization experiments indicate that the slug/snail family of transcription factors functions overall as an epithelial phenotype repressor and could represent a key EMT contributor. BioEssays 23:912–923, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The ectoplasmic specialization (ES) is a testis‐specific, actin‐based hybrid anchoring and tight junction. It is confined to the interface between Sertoli cells at the blood–testis barrier, known as the basal ES, as well as between Sertoli cells and developing spermatids designated the apical ES. The ES shares features of adherens junctions, tight junctions and focal contacts. By adopting the best features of each junction type, this hybrid nature of ES facilitates the extensive junction‐restructuring events in the seminiferous (...) epithelium during spermatogenesis. For instance, the α6β1‐integrin–laminin 333 complex, which is usually limited to the cell–matrix interface in other epithelia to facilitate cell movement, is a putative apical ES constituent. Furthermore, JAM‐C and CAR, two tight junction integral membrane proteins, are also components of apical ES involving in spermatid orientation. We discuss herein the mechanisms that maintain the cross‐talk between ES and blood–testis barrier to facilitate cell movement and orientation in the seminiferous epithelium. BioEssays 29: 36–48, 2007. © 2006 Wiley Periodicals, Inc. (shrink)

Cell shape and cell contacts are determined by transmembrane receptor‐mediated associations of the cytoskeleton with specific extracellular matrix proteins and with ligands on the surface of adjacent cells. The cytoplasmic domains of these microfilament‐membrane associations at the adherens junction sites, also Iocalize a variety of regulatory molecules involved in signal transduction and gene regulation. The stimulation of cells with soluble polypeptide factors leads to rapid changes in cell shape and microfilament component organization. In addition, this stimulation also activates the (...) phosphoinositide signaling pathway. Recently, a linkage between actin‐binding proteins and the phosphoinositide signaling pathway, was discovered. It is Suggested that by the association with the second messenger system, and/or by controlling the localization of regulatory molecules, the cytoskeleton may regulate gene expression. (shrink)

Somatic or inherited mutations in the adenomatous polyposis coli (APC) gene are a frequent cause of colorectal cancer in humans. APC protein has an important tumor suppression function to reduce cellular levels of the signaling protein β‐catenin and, thereby, inhibit β‐catenin and T‐cell‐factor‐mediated gene expression. In addition, APC protein binds to microtubules in vertebrate cells and localizes to actin‐rich adherens junctions in epithelial cells of the fruit fly Drosophila (Fig. 1). Very little is known, however, about the function (...) of these cytoskeletal associations. Recently, Hamada and Bienz have described a potential role for Drosophila E‐APC in cellular adhesion,1 which offers new clues to APC function in embryonic development, and potentially colorectal adenoma formation and tumor progression in humans. BioEssays 24:771–774, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

RAS GTPases play essential roles in normal development and are direct drivers of human cancers. Three decades of study have failed to wholly characterize pathways stimulated by activated RAS, driven by engagement with ‘effector’ proteins that have RAS binding domains (RBDs). Bone fide effectors must bind directly to RAS GTPases in a nucleotide‐dependent manner, and this interaction must impart a clear change in effector activity. Despite this, for most proteins currently deemed effectors there is little mechanistic understanding of how binding (...) to the GTPase alters protein function. There has also been limited effort to comprehensively resolve the specificity of effector binding to the full array of RAS superfamily GTPase proteins. This review will summarize what is known about RAS‐driven activation for an array of potential effector proteins, focusing on structural and mechanistic effects and highlighting how little is still known regarding this key paradigm of cellular signal transduction. (shrink)

In this essay we take the view that too much reality has been afforded to the notion of ‘particles’ and to ‘flow of supercurrent,’ in the superconducting state. Instead we take the original point of view of Josephson that “ It is clear that intuition is of no great help in understanding the supercurrent as a flow of Cooper pairs “ which is more akin to, and in line with, a “telegraphing of amplitudes” approach. With this conception in mind, we (...) examine the results of Jillie et al and Smith et al. of two Josephson junctions connected in series by a superconducting join. We argue that their results can best be understood in terms of the entanglement of current elements via the interfering of amplitudes. We sketch an approach to calculating the current spanning two entangled Josephson junctions, which reduces to the relation for a single junction when the current is set zero in either of the pair, or the entanglement ceases. We speculate that if this interfering of amplitudes was found to persist, after the separation of the junctions in space, there still remaining a connection in their common past, then this would furnish, at least the possibility, of a new means of signalling without wires. Experiments are suggested. (shrink)

Gap junctions are ubiquitous plasma membrane specializations that allow cells to exchange small molecules and ions directly. The isolation, biochemical characterization and molecular cloning of the major protein of rat liver gap junctions lead to a clearer view of these membrane zones that allow cells to ‘talk’ to each other and co‐ordinate their activities in tissues and organs.

The field programmable gate array implementation of the nonlinear resistor-capacitor-inductor shunted Josephson junction model and its application to sEMG signal encryption through image encrypted technique are reported in this study. Thanks to the numerical simulations and FPGA implementation of the NRCISJJ model, different shapes of chaotic attractors are revealed by varying the parameters. The chaotic behaviour found in the NRCISJJ model is used to encrypt the sEMG signal through image encryption technique. The results obtained are interesting and open up many (...) perspectives. (shrink)

Most parts of the brain are conserved across reptiles and birds (sauropsids) and mammals. Two major qualitative differences occur in the upper part, or pallium, of the telencephalon, the most rostral part of the brain. Mammals have a six‐layered neocortex and also exhibit a different morphological organization in the lateral half, or sector, of their pallium than do sauropsids. These differences of lateral pallial construction may derive from small but crucial differences in migration patterns of neuronal precursors generated at or (...) above the corner of the lateral ventricle, the corticostriatal junction (CS). Sauropsids have a large structure, the dorsal ventricular ridge, that is proliferated from this region, and its anterior part (ADVR) receives ascending projections from the dorsal thalamus. Mammals have multiple structures in this same region—the lateral part of neocortex, amygdala, and claustrum‐endopiriform formation. We propose here that, as the degree of development of structures that form the deeper tier of the pallium varies across the stages of embryology and across phylogeny, mutations may have occurred during evolution at the origin of mammals that had profound consequences for the fate of neural populations generated in the region of the CS and its neighboring pallial germinal zone. BioEssays 24:530–541, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

The right temporoparietal junction (rTPJ) and dorsomedial prefrontal cortex (dmPFC), which are involved in social cognition, have been proposed to play key roles in guiding human altruistic behavior. However, no study has provided empirical evidence that the rTPJ and dmPFC play distinct roles in altruism under situations of inequality. A total of 107 healthy young adults were randomly assigned to receive anodal or sham transcranial direct current stimulation (tDCS) to either the dmPFC or rTPJ, and they participated in a modified (...) dictator game. The stimulation of the dmPFC increased the level of altruistic behavior, while the stimulation of the rTPJ did not. Furthermore, we determined that the increase in altruism induced by tDCS of the dmPFC could be modulated by perspective taking. These results demonstrate that the dmPFC and rTPJ play distinct roles in the enhancement of altruism in situations of inequality; this finding is consistent with theories proposing that the dmPFC has evolved mechanisms dedicated to perspective taking. (shrink)

Gap junction intercellular communication channels permit the exchange of small regulatory molecules and ions between neighbouring cells and coordinate cellular activity in diverse tissue and organ systems. These channels have short half‐lives and complex assembly and degradation pathways. Much of the recent work elucidating gap junction biogenesis has featured the use of connexins (Cx), the constituent proteins of gap junctions, tagged with reporter proteins such as Green Fluorescent Protein (GFP) and has illuminated the dynamics of channel assembly in live (...) cells by high‐resolution time‐lapse microscopy. With some studies, however, there are potential short‐comings associated with the GFP chimeric protein technologies. A recent report by Gaietta et al., has highlighted the use of recombinant proteins with tetracysteine tags attached to the carboxyl terminus of Cx43, which differentially labels ‘old’ and ‘new’ connexins thus opening up new avenues for studying temporal and spatial localisation of proteins and in situ trafficking events.1 BioEssays 24:876–880, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Our prior research demonstrated that the right temporoparietal junction exerted a modulatory role in ingroup bias in emotional mimicry. In this study, two experiments were conducted to further explore whether the rTPJ is a neural region for emotional mimicry or for the modulation of emotional mimicry by group membership in a sham-controlled, double-blinded, between-subject design. Both experiments employed non-invasive transcranial direct current stimulation to temporarily change the cortical excitability over the rTPJ and facial electromyography to measure facial muscle activations as (...) an index of emotional mimicry. After the anodal or sham stimulation, participants in Experiment 1 passively viewed a series of happy clips, while participants in Experiment 2 viewed happy clips performed by ethnic ingroup and outgroup models. fEMG analyses revealed that participants in Experiment 1 showed the same degree of happy mimicry for both tDCS conditions and participants in Experiment 2 showed an ingroup bias in happy mimicry in the sham condition, which disappeared in the anodal condition. Taken together, the present study demonstrated that rTPJ plays a role in the modulation of emotional mimicry by group membership. (shrink)

This article develops a conceptual pattern of the reasons and scope of business responsibility for modern slavery. It introduces modern slavery as either relation or structure and designs an understanding of a broad and a narrow model of business responsibility, consisting of business power, internal and external realms of business conduct and public and private roles of companies. Crossing the two models of modern slavery with the two models of business responsibility, the article carves out the strengths and limits of (...) their junctions. The continuous pendulum between the junctions allows to discuss how and why companies can be responsible for modern slavery. It thus contributes analytically, practically and normatively to tackling modern slavery. (shrink)

We propose that interaction rules derived from polyamine exchange in connected cells may explain the spatio‐temporal organization of gap junctions observed during tissue regeneration and tumorigenesis. We also hypothesize that polyamine exchange can be considered as signal that allows cells to sense the proliferation status of their neighbors. Polyamines (putrescine, spermidine, and spermine) are indeed small aliphatic polycations that serve as fuels to sustain elevated proliferation rates of the order observed in cancer cells. Based on recent reports, we consider (...) here that polyamines can be exchanged through gap junction channels between mammalian cells. Such intercellular exchange of polyamines has critical consequences on the local control of growth. In line with this hypothesis, the complex protein network that keeps polyamine levels finely tuned in mammalian cells can translate polyamine efflux or influx into integrated signals controlling transcription, translation, and cell communications. (shrink)

When we judge an action as morally right or wrong, we rely on our capacity to infer the actor's mental states. Here, we test the hypothesis that the right temporoparietal junction, an area involved in mental state reasoning, is necessary for making moral judgments. In two experiments, we used transcranial magnetic stimulation to disrupt neural activity in the RTPJ transiently before moral judgment and during moral judgment. In both experiments, TMS to the RTPJ led participants to rely less on the (...) actor's mental states. A particularly striking effect occurred for attempted harms : Relative to TMS to a control site, TMS to the RTPJ caused participants to judge attempted harms as less morally forbidden and more morally permissible. Thus, interfering with activity in the RTPJ disrupts the capacity to use mental states in moral judgment, especially in the case of attempted harms. (shrink)

The intercellular junctions connecting the cytoplasms of fibre cells in the mammalian lens have until recently been regarded as a class of junction which is fundamentally different from that of the gap junctions in other organs. Recent observations, however, suggest that the lens junctions fit protein topology predictions common for all gap junctions. While the homologous peptide portions are predicted to form the channels, the divergent peptide portions of the gap junction polypeptides may adapt channel activity (...) to the special tissue requirements. (shrink)

Neuronal information processing depends on converting membrane depolarizations into compartmentalized biochemical signals that can modify neuronal activity and structure. However, our understanding of how neurons translate electrical signals into specific biochemical responses remains limited, especially in the soma where gene expression and ion channel function are crucial for neuronal activity. Here, I emphasize the importance of physically compartmentalizing action potential‐triggered biochemical reactions within the soma. Emerging evidence suggests that somatic endoplasmic reticulum–plasma membrane (ER‐PM) junctions are specialized organelles that coordinate (...) electrical and biochemical signaling. The juxtaposition of ion channels and signaling proteins at a prominent subset of these sites enables compartmentalized calcium and cAMP‐dependent protein kinase (PKA) signaling. I explore the hypothesis that these PKA‐containing ER‐PM junctions serve as critical sites for translating membrane depolarizations into PKA signals and identify key gaps in knowledge of the assembly, regulation, and neurobiological functions of this somatic signaling system. (shrink)

The omnipresence of information and its role of the central/basic element within different contexts represents one of the main characteristics of our contemporaneity. In everydayness of inauthentic Da-sein the amount of pure information obscures deeper questions; nevertheless, the understanding of its role is crucial for the contemporary approach towards interpreting phenomena in our environment. Transfer of the concept of information is therefore crucial for the contemporary description of physical reality, evolution and for contemporary construction of the subjective time and its (...) link with the objective one, while its multiple connections with contemporary space-time can be most directly seen in literature. Reflection of these transfers by combining and rethinking their findings consequently emphasizes the vanishing border between different fields and makes complex, clear and contemporary review of the question and the partly constructed answer of us and our environment possible. (shrink)

Members of the CAR group of Ig‐like type I transmembrane proteins mediate homotypic cell adhesion, share a common overall extracellular domain structure and are closely related at the amino acid sequence level. CAR proteins are often found at tight junctions and interact with intracellular scaffolding proteins, suggesting that they might modulate tight junction assembly or function. However, impairment of tight junction integrity has not been reported in mouse knockout models or zebrafish mutants of CAR members. In contrast, in the (...) same knockout models deficits in gap junction communication were detected in several organ systems, including the atrioventricular node of the heart, smooth muscle cells of the intestine and the ureter and in Sertoli cells of the testes. Possible interactions between BT‐IgSF and connexin41.8 on the disturbed pattern of pigment stripes found in zebrafish mutants and between ESAM and connexin43 during hematopoiesis in the mouse are also discussed. On the basis of the combined data and phenotypic similarities between CAR member mutants and connexin mutants I hypothesize that they primarily play a role in the organization of gap junction communication. Also see the video abstract here: https://youtu.be/i0yq2KhuDAE. (shrink)

Behaviorally, children’s explicit theory of mind (ToM) proceeds in a progression of mental-state understandings: developmentally, children demonstrate accurate explicit desire-reasoning before accurate explicit belief-reasoning. Given its robust and cross-cultural nature, we hypothesize this progression may be paced in part by maturation/specialization of the brain. Neuroimaging research demonstrates that the right temporoparietal junction (TPJ) becomes increasingly selective for ToM reasoning as children age, and as their ToM improves. But this research has narrowly focused on beliefs or on undifferentiated mental-states. A recent (...) ERP study in children included a critical contrast to desire-reasoning, and demonstrated that right posterior potentials differentiated belief-reasoning from desire-reasoning. Taken together, the literature suggests that children’s desire-belief progression may be paced by specialization of the right TPJ for belief-reasoning specifically, beyond desire-reasoning. In the present study, we tested this hypothesis directly by examining children’s belief- and desire-reasoning using functional near-infrared spectroscopy in conjunction with structural magnetic resonance imaging to pinpoint brain activation in the right TPJ. Results showed greatest activation in the right TPJ for belief-reasoning, beyond desire-reasoning, and beyond non-mental reasoning (control). Findings replicate and critically extend prior ERP results, and provide clear evidence for a specific neural mechanism underlying children’s progression from understanding desires to understanding beliefs. (shrink)

DNA junctions are by‐products of recombinational repair, during which a damaged DNA sequence, assisted by RecA filament, invades an intact homologous DNA to form a joint molecule. The junctions are three‐strand or four‐strand depending on how many single DNA strands participate in joint molecules. In E. coli, at least two independent pathways to remove the junctions are proposed to operate. One is via RuvAB‐promoted migration of four‐strand junctions with their subsequent resolution by RuvC. In vivo, RuvAB (...) and RuvC enzymes might work in a single complex, a resolvasome, to clean DNA from used RecA filaments and to resolve four‐strand junctions. An alternative pathway for junction removal could be via RecG‐promoted branch migration of three‐strand junctions, provided that an as yet uncharacterized endonuclease activity incises one of the strands in the joint molecules. (shrink)

ObjectivesTo simulate hemodynamic changes after extraluminal compression in pulsatile tinnitus patients with a prominent transverse-sigmoid sinus junction.MethodsOne patient-specific case was reconstructed based on computed tomography venography images of a PT patient. The compression degree served as a new index in this study. Cases with 10, 20, 30, 40, 50, 60, 70, 80, and 90% of the compression degree of the control subject were constructed. Steady-state computational fluid dynamics were assessed. The wall pressure distribution, wall maximum pressure and flow pattern of (...) the PTSJ were calculated to evaluate hemodynamic differences among all cases.ResultsWith increasing compression, the wall pressure at the compression point and downstream of the PTSJ decreased but increased upstream. When the compression degree exceeded 70%, the upstream pressure increased significantly. Above 50% compression, the blood flow pattern downstream of the sigmoid sinus tended to spiral, especially after 80% compression. Beyond 60% compression, the blood flow pattern under the compression axis became more medial.ConclusionMechanical compression of PTSJ changes wall pressure and blood flow patterns. The degree of compression should be carefully observed to avoid possible complications or reoccurrence. (shrink)

This paper outlines limitations to integrating social meaning into cognitive models of speech production and processing. The authors remind the reader that acoustic space is not the same as articulatory or auditory space and they point to the benefits of using relatively uncommon dynamic methods of acoustic analysis. Further, the authors argue in favor of a more complex and socially‐informed conception of ‘style’ than is typically used in work on language cognition.

The meaning of a noun phrase like ‘brown cow’, or ‘cow that ate grass’, is somehow conjunctive. But conjunctive in what sense? Are the meanings of other phrases—e.g, ‘ate quickly’, ‘ate grass’, and ‘at noon’—similarly conjunctive? I suggest a possible answer, in the context of a broader conception of natural language semantics. But my main aim is to highlight some underdiscussed questions and some implications of our ignorance.

The neuromuscular junction has been used for several decades as an excellent model system to examine the cellular and molecular events involved in the formation and maintenance of a differentiated chemical synapse. In this context, several laboratories have focused their efforts over the last 15 years on the important contribution of transcriptional mechanisms to the regulation of the development and plasticity of the postsynaptic apparatus in muscle fibers. Converging lines of evidence now indicate that post‐transcriptional events, operating at the level (...) of mRNA stability and targeting, are likely to also play key roles at the neuromuscular junction. Here, we present the recent findings highlighting the role of these additional molecular events and extend our review to include data showing that post‐transcriptional events are also important in the control of the expression of genes encoding synaptic proteins in muscle cells placed under different conditions. Finally, we discuss the possibility that mis‐regulation of post‐transcriptional events can occur in certain neuromuscular diseases and cause abnormalities of the neuromuscular junction. BioEssays 25:25–31, 2003. © 2002 Wiley Periodicals, Inc. (shrink)

Ductin is the highest conserved membrane protein yet found in eukaryotes. It is multifunctional, being the subunit c or proteolipid component of the vacuolar H+‐ATPase and at the same time the protein component of a form of gap junction in metazoan animals. Analysis of its structure shows it to be a tandem repeat of two 8‐kDa domains derived from the subunit c of the F0 proton pore from the F1F0 ATPase. Each domain contains two transmembrane α‐helices, which together may form (...) a four‐helix bundle. In both the V‐ATPase and gap junction channel, ductin is probably arranged as a hexamer of subunits forming a central channel of gap junction‐like proportions. The two functions appear to be seggregated by ductin having two orientations in the bilayer. Ductin is also the major component of the mediatophore, a protein complex which may aid in the release of neurotransmitters across the pre‐synaptic membrane. It is also a target for a class of poorly understood viral polypeptides. These polypeptides are small and highly hydrophobic and some have oncogenic activity. Ductin thus appears to be at the crossroads of a number of biological processes. (shrink)

During late embryonic and early postnatal development, synaptic connections are extensively modified so that some functional connections are weakened and eliminated from a neural circuit while others are strengthened and maintained. The mechanisms that underlie synapse elimination are beginning to be understood from studies of the neuromuscular junction. A recent paper(1) provides some intriguing insights into the role proteases may play in the developmental disassembly of neuromuscular synapses.