Yoshimi Takai

....

..In this article, the roles and modes of action of nectins and necls in cell adhesion, migration, and polarization are reviewed...

..The adhesion system is furthermore involved in the formation of synapses in neurons and the organization of heterotypic junctions between Sertoli cells and spermatids in the testis...

..Cascades and cross-talks of small G proteins have also been clarified. In this review, functions of small G proteins and their modes of activation and action are described...

..Intercellular adhesion through nectins induces activation of Cdc42 and Rac small G proteins, leading to a reorganization of the actin cytoskeleton, gene expression, and cell polarization...

..It has been shown that reorganization of actin filaments is also involved in Ca2+-dependent exocytosis. Therefore, rabphilin-3A may serve as a linker for Rab3A and cytoskeleton...

....

..Thus, nectin regulates the assembly and cell-cell adhesion activity of E-cadherin through afadin, nectin signaling, and p120(ctn) for the formation of AJs in Madin-Darby canine kidney cells...

..These results suggest that nectins and afadin are involved in dynamic epithelial remodeling during mouse development...

..These results indicate the unique localization of Necl-2 and its possible involvement in localization of a transmembrane protein(s) through Pals2...

..These results indicate that the contacts between the commissural axons and the floor plate cells are mediated by the hetero-trans-interaction between nectin-1 and -3 and involved in regulation of the trajectory of the commissural axons...

..These results indicate that nectin-1 and -3 are involved in the localization of PAR-3 at AJs in the neuroepithelial cells of the embryonic telencephalon...

..Thus, Tage4 heterophilically trans-interacts with nectin-3 and regulates cell migration. Tage4 is tentatively re-named here nectin-like molecule-5 (necl-5) on the basis of its function and domain structure similar to those of nectins...

..Cdc42 activated through c-Src then enhanced the GEF activity of tyrosine-phosphorylated Vav2 on Rac1. These results indicate that Vav2 is a GEF responsible for the nectin-induced, c-Src-, and Cdc42-mediated activation of Rac...

..Thus, Necl-5 has a critical role in integrin alphavbeta3 clustering and focal complex formation...

..We furthermore show here that enhanced motility and metastasis of V12Ras-NIH3T3 cells are at least partly the result of up-regulated Necl-5...

..Thus, the interaction of PDZ-GEF1 with an internalized neurotrophin receptor transported to late endosomes induces sustained activation of both Rap1 and ERK and neurite outgrowth...

..Knockdown of RA-RhoGAP reduced the Rap1-induced neurite outgrowth. These results indicate that RA-RhoGAP transduces a signal from Rap1 to Rho and regulates the neurite outgrowth...

..These results indicate that LMO7 is an afadin- and alpha-actinin-binding protein that connects the nectin-afadin and E-cadherin-catenin systems through alpha-actinin...

..We have found that two more proteins are co-immunoprecipitated with Rab3 GEP from the CSV fraction of rat brain. We attempted here to isolate and characterize one of them...

..These results indicate that RIN2 connects Ras to Rab5 in the HGF-induced endocytosis of E-cadherin...

..These results indicate that Necl-5 plays roles not only in cell motility but also in cell proliferation...

....

..ADIP may connect the nectin-afadin and E-cadherin-catenin systems through alpha-actinin, and ADIP may be involved in organization of the actin cytoskeleton at AJs through afadin and alpha-actinin...

..These results suggest that nectin has a role in the localization of JAM at TJs in the process of the formation of the junctional complex in epithelial cells...

..Thus, integrin alpha(v)beta3 and nectin play pivotal roles in the cross-talk between cell-matrix and cell-cell junctions and the formation of cadherin-based AJs...

..In addition, the abnormal mossy fiber trajectory was observed. These results indicate that nectins are involved in the formation of PAJs, which maintain the proper mossy fiber trajectory...

..These results indicate a key role of Necl-5 in directional cell movement by physically and functionally interacting with both integrin alpha(v)beta(3) and PDGF receptor...

..This complex was associated with PDGF receptor on the plasma membrane at cell-cell adhesion sites. Thus, the nectin-afadin complex is involved in PDGF-induced cell survival, at least through the PI3K-Akt signaling pathway...

..Thus, tomosyn demarcates the plasma membrane by binding to syntaxin-1 phosphorylated by ROCK, and thereby regulates extension and retraction of neurites...

..S-SCAM has been suggested to be a component of PSDs, but its precise localization at the synapses remains unknown...

..These results indicate that the down-regulation of Necl-5 induced by its interaction with nectin-3 upon cell-cell contacts may be at least one mechanism underlying contact inhibition of cell movement and proliferation...

..These results indicate that nectins regulate the velocity of the formation of the E-cadherin-based AJs and the subsequent formation of the claudin-based TJs...

..Thus, Necl-5 and Sprouty2 cooperatively regulate PDGF-induced Ras signaling. The roles of Necl-5 and Sprouty2 in contact inhibition for cell proliferation are also discussed...

..These results indicate that the actin cytoskeleton is required for the association of the nectin-afadin unit with other CAMs and PMPs at AJs and TJs...

..Thus, nectin plays a role in the formation of E-cadherin-based AJs in keratinocytes...

..Furthermore, nectin interacts in trans with nectin-like molecule-5 (Necl-5) and regulate cell movement and proliferation. We describe cooperative roles of nectins with other CAMs and growth factor receptors...

..These results indicate that ZO-1 colocalizes with nectin and afadin at the PAs and that the nectin-afadin system is involved in the localization of ZO-1...

..These results indicate that the Cdc42 activated by the trans-interactions of nectins is involved in the organization of AJs and TJs in different mechanisms in MDCK cells...

..Thus, afadin plays a critical role in the proper regulation of the PDGF-induced activation of PDGF receptor and signaling by Ras-ERK. This effect, which is mediated by SHP-2, impacts cellular morphology...

..These results indicate that nectin is involved in the localization of IQGAP1 at AJs through the actin cytoskeleton...

..These results indicate that the trans-interactions of Necl-5 and nectin-3 and of nectin and nectin induce the activation of Cdc42 and Rac through the common signaling molecules c-Src, Rap1, FRG, and Vav2...

..These results indicate a novel role of nectins in regulation of the E-cadherin-induced activation of Rac and formation of cell-cell AJs...

..We describe here the roles and modes of action of nectins as CAMs...

..Knockdown of annexin II by RNA interference also inhibited the re-concentration of E-cadherin. These results indicate that the annexin II-S100A10 complex is involved in the formation of the E-cadherin-based AJs in MDCK cells...

..We describe here these novel roles of Par-3 in the formation of junctional complexes...

..These results indicate that Rap1 is activated by nectins through the c-Src-Crk-C3G signaling and involved in the nectin-induced, c-Src- and FRG-mediated activation of Cdc42 and formation of AJs...

....

..Here we describe how subcellular protein interactions are coordinated to induce changes in actin organization and dynamics, in response to the status of apical junctions...

..These results indicate that nectin-1 plays a key role in the expression of loricrin in the epidermis...

..These results indicate the important role of the Rac/Cdc42-IQGAP1 system in the dynamic organization and maintenance of the E-cadherin-based AJs...

..In addition, expression of the gene encoding nectin-3 is markedly reduced in transformed cells. Thus, up-regulation of Necl-5 following transformation contributes to the loss of contact inhibition in transformed cells...

..CONCLUSION: These results indicate that Cdc42 and Rac activated by the trans-interaction of nectins selectively induce the activation of JNK, but are not essential for the association of nectins and cadherin to form AJs in fibroblasts...

..To obtain evidence for this role of nectin, we attempted to develop an antagonist and/or agonist of nectin...

..These results indicate that afadin organizes the formation of cell-cell junctions by regulating cell polarization in early embryonic development...

..NuMA complex. These results indicate that Lgl2 forms a Lgl2.Par-6.aPKC.LGN complex, which responds to mitotic signaling to establish normal cell division...

..These results indicate that Necl-5 plays roles not only in cell motility and proliferation but also in cell-cell adhesion in cooperation with nectin-3...

..These results indicate that the heterophilic trans-interaction between nectin-2 and nectin-3 is essential for the formation and maintenance of Sertoli-spermatid junctions that plays a critical role in spermatid development...

..These findings suggest that afadin plays crucial roles, independently of the role as the nectin-afadin module, in barrier function and homeostasis of the intestinal epithelia once the epithelial structure has been established...

....

..We describe the roles and modes of action of PKA and tomosyn in Ca2+-dependent neurotransmitter release...

..These results indicate that the expression of mouse Necl-5 is induced by FGF or V12Ki-Ras through the Raf-MEK-ERK-AP-1 pathway...

..These results indicate that, in contrast with the previous notion, our structure represents a cis-dimer. Thus, our findings clearly reveal the structural basis for the cis-dimerization of nectins through the first Ig-like domains...

..These results indicate that the transient interaction of afadin with ZO-1 is necessary for the formation of TJs in MDCK cells...

..Nectin-3 required afadin, a nectin- and F-actin-binding protein, for this ability. In conclusion, nectin plays a novel role in the co-localization of JAM and claudin at the same CAMD...

..The amino acid sequence analysis of this 30 KDa protein revealed that it is GTP cyclohydrolase I...

..mLin-7 did not directly interact with nectin or afadin. The results indicate that mLin-7 localizes at cell-cell junctions through the nectin-afadin system...

....

..These results indicate that the nectin-afadin system plays essential roles in coupling cell-cell adhesion and the cortical actin scaffold at SspJs and in subsequent sperm morphogenesis...

..These results indicate that Rab3 GEP and GAP are colocalized with Rab3A at the synaptic release sites and suggest that they regulate the activity of Rab3A and are involved in Ca2+-dependent exocytosis...

..The Rabphilin-3A-interacting protein also binds to protein kinase C in the presence of Ca2+ and phosphatidylserine. These results indicate that Rabphilin-3A binds to beta-adducin in the presence of Ca2+ and phosphatidylserine...

..These effects of nectins require their cytoplasmic tail but not their association with afadin. We propose here the functional relationship between nectins and the small G proteins in the organization of AJs...

..We studied the roles of the Rho family small G proteins in invadopodia formation...

..Here we summarize our knowledge of nectins and Necls and discuss cell adhesion biology in the kidney...

..These results suggest that tomosyn is an important component in the neurotransmitter release process where it may stimulate SNARE complex formation...

..The gold wire was rather stable for a few seconds under strong electron beam illumination...

..These results indicate that Bnr1p directly interacts with Hof1p as well as with profilin to regulate cytoskeletal functions in S. cerevisiae...

..These results show that Rabphilin-3A is involved in Ca(2+)-dependent CG exocytosis at fertilization in mouse eggs...

....

..CONCLUSIONS: These results suggest a role of the nectin-afadin system in the organization of TJs as well as AJs in epithelial cells...

....

..This region was necessary but not sufficient for high-affinity binding of tomosyn to syntaxin-1...

..These results suggest that ERM as well as Rho GDI and the Rho GDP/GTP exchange factor are involved in the activation of the Rho subfamily members, which then regulate reorganization of actin filaments through the ERM system...

....

..These results indicate that Bni1p and Bnr1p are potential targets of the Rho family members, interact with profilin and regulate the reorganization of actin cytoskeleton...

..Thus, radixin plays an important role in activation of the Rho family members by recruiting their positive and negative regulators...

..These results indicate that Bem4p is a novel protein directly interacting with Rho1p and is involved in the RHO1-mediated signaling pathway...

..These results indicate that both Rho1p and Spa2p are involved in the localization of Bni1p at the growth sites where Rho1p regulates reorganization of the actin cytoskeleton through Bni1p...

..These results indicate that there are at least two signaling pathways regulated by Rho1p and that one of the downstream targets is Pkc1p, leading to the activation of the MAP kinase cascade...

..Rabphilin-11 turned out to be a rat counterpart of recently reported bovine Rab11BP. These results indicate that rabphilin-11 is a downstream target of Rab11 which is involved in vesicle recycling...

..These results indicate that the rabphilin-11-mSec13p interaction is implicated in vesicle trafficking...

..Furthermore, this synthetic lethality was caused by the incapability of RhoA to activate Pkc1p, but not glucan synthase. These results suggest that Rho1p regulates cytoskeletal reorganization at least through Bni1p and Pkc1p...

..Thus, both nectin and Necl family members play important roles in fundamental cellular functions, including cell adhesion, polarization, movement, and proliferation...

..Here, we focus on how the activity of Cdc42 and Rac induced by trans-interacting nectin is examined by use of the pull-down and the cell-spreading assays...

..Therefore, the trans-interaction of nectin essentially functions in the inactivation of integrin at AJs through the PTPmu-induced inactivation of PIPKIgamma...

..Although DH and PH1 show exchange activity, FAB, in addition to DH and PH1, is required for the formation of microspikes, whereas FYVE and PH2, in addition to DH and PH1, are required for the formation of lamellipodia...

..Here, we describe the assay method for the endocytosis of E-cadherin from the AJ-enriched fraction prepared from rat liver...

..These results suggest that an unidentified mechanism, by which nectin and E-cadherin form the actin cytoskeleton-associated adherens junctions to form strong cell-cell adhesion, is impaired in HSC-39 cells...

..We show here that the second Ig-like loop is essential for the cis-dimer formation of nectin on the same cell, and that the cis-dimer formation is essential for the trans-dimer formation...