Ebnet K, Aurrand-Lions M, Kuhn A, Kiefer F, Butz S, Zander K, Meyer zu Brickwedde MK, Suzuki A, Imhof BA, Vestweber D.; ''The junctional adhesion molecule (JAM) family members JAM-2 and JAM-3 associate with the cell polarity protein PAR-3: a possible role for JAMs in endothelial cell polarity.''; PubMedEurope PMCScholia
Dantzig AH, Hoskins JA, Tabas LB, Bright S, Shepard RL, Jenkins IL, Duckworth DC, Sportsman JR, Mackensen D, Rosteck PR.; ''Association of intestinal peptide transport with a protein related to the cadherin superfamily.''; PubMedEurope PMCScholia
Zhang Y, Tu Y, Gkretsi V, Wu C.; ''Migfilin interacts with vasodilator-stimulated phosphoprotein (VASP) and regulates VASP localization to cell-matrix adhesions and migration.''; PubMedEurope PMCScholia
Pellissier F, Gerber A, Bauer C, Ballivet M, Ossipow V.; ''The adhesion molecule Necl-3/SynCAM-2 localizes to myelinated axons, binds to oligodendrocytes and promotes cell adhesion.''; PubMedEurope PMCScholia
Wang X, Fukuda K, Byeon IJ, Velyvis A, Wu C, Gronenborn A, Qin J.; ''The structure of alpha-parvin CH2-paxillin LD1 complex reveals a novel modular recognition for focal adhesion assembly.''; PubMedEurope PMCScholia
Padhi AK, Banerjee K, Gomes J, Banerjee M.; ''Computational and functional characterization of Angiogenin mutations, and correlation with amyotrophic lateral sclerosis.''; PubMedEurope PMCScholia
Yamaji S, Suzuki A, Kanamori H, Mishima W, Yoshimi R, Takasaki H, Takabayashi M, Fujimaki K, Fujisawa S, Ohno S, Ishigatsubo Y.; ''Affixin interacts with alpha-actinin and mediates integrin signaling for reorganization of F-actin induced by initial cell-substrate interaction.''; PubMedEurope PMCScholia
Kaufman L, Yang G, Hayashi K, Ashby JR, Huang L, Ross MJ, Klotman ME, Klotman PE.; ''The homophilic adhesion molecule sidekick-1 contributes to augmented podocyte aggregation in HIV-associated nephropathy.''; PubMedEurope PMCScholia
Tu Y, Huang Y, Zhang Y, Hua Y, Wu C.; ''A new focal adhesion protein that interacts with integrin-linked kinase and regulates cell adhesion and spreading.''; PubMedEurope PMCScholia
Lopez M, Aoubala M, Jordier F, Isnardon D, Gomez S, Dubreuil P.; ''The human poliovirus receptor related 2 protein is a new hematopoietic/endothelial homophilic adhesion molecule.''; PubMedEurope PMCScholia
Yamagata M, Weiner JA, Sanes JR.; ''Sidekicks: synaptic adhesion molecules that promote lamina-specific connectivity in the retina.''; PubMedEurope PMCScholia
Dong X, Xu F, Gong Y, Gao J, Lin P, Chen T, Peng Y, Qiang B, Yuan J, Peng X, Rao Z.; ''Crystal structure of the V domain of human Nectin-like molecule-1/Syncam3/Tsll1/Igsf4b, a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule.''; PubMedEurope PMCScholia
Hopkinson SB, Jones JC.; ''The N terminus of the transmembrane protein BP180 interacts with the N-terminal domain of BP230, thereby mediating keratin cytoskeleton anchorage to the cell surface at the site of the hemidesmosome.''; PubMedEurope PMCScholia
de Pereda JM, Lillo MP, Sonnenberg A.; ''Structural basis of the interaction between integrin alpha6beta4 and plectin at the hemidesmosomes.''; PubMedEurope PMCScholia
Mishima W, Suzuki A, Yamaji S, Yoshimi R, Ueda A, Kaneko T, Tanaka J, Miwa Y, Ohno S, Ishigatsubo Y.; ''The first CH domain of affixin activates Cdc42 and Rac1 through alphaPIX, a Cdc42/Rac1-specific guanine nucleotide exchanging factor.''; PubMedEurope PMCScholia
LaLonde DP, Brown MC, Bouverat BP, Turner CE.; ''Actopaxin interacts with TESK1 to regulate cell spreading on fibronectin.''; PubMedEurope PMCScholia
Lorenz S, Vakonakis I, Lowe ED, Campbell ID, Noble ME, Hoellerer MK.; ''Structural analysis of the interactions between paxillin LD motifs and alpha-parvin.''; PubMedEurope PMCScholia
Rosenberger G, Jantke I, Gal A, Kutsche K.; ''Interaction of alphaPIX (ARHGEF6) with beta-parvin (PARVB) suggests an involvement of alphaPIX in integrin-mediated signaling.''; PubMedEurope PMCScholia
Michel D, Arsanto JP, Massey-Harroche D, Béclin C, Wijnholds J, Le Bivic A.; ''PATJ connects and stabilizes apical and lateral components of tight junctions in human intestinal cells.''; PubMedEurope PMCScholia
Masuda M, Yageta M, Fukuhara H, Kuramochi M, Maruyama T, Nomoto A, Murakami Y.; ''The tumor suppressor protein TSLC1 is involved in cell-cell adhesion.''; PubMedEurope PMCScholia
Kakunaga S, Ikeda W, Itoh S, Deguchi-Tawarada M, Ohtsuka T, Mizoguchi A, Takai Y.; ''Nectin-like molecule-1/TSLL1/SynCAM3: a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule localizing at non-junctional contact sites of presynaptic nerve terminals, axons and glia cell processes.''; PubMedEurope PMCScholia
Tu Y, Wu S, Shi X, Chen K, Wu C.; ''Migfilin and Mig-2 link focal adhesions to filamin and the actin cytoskeleton and function in cell shape modulation.''; PubMedEurope PMCScholia
Takahashi K, Nakanishi H, Miyahara M, Mandai K, Satoh K, Satoh A, Nishioka H, Aoki J, Nomoto A, Mizoguchi A, Takai Y.; ''Nectin/PRR: an immunoglobulin-like cell adhesion molecule recruited to cadherin-based adherens junctions through interaction with Afadin, a PDZ domain-containing protein.''; PubMedEurope PMCScholia
Hannigan GE, Leung-Hagesteijn C, Fitz-Gibbon L, Coppolino MG, Radeva G, Filmus J, Bell JC, Dedhar S.; ''Regulation of cell adhesion and anchorage-dependent growth by a new beta 1-integrin-linked protein kinase.''; PubMedEurope PMCScholia
Mueller S, Wimmer E.; ''Recruitment of nectin-3 to cell-cell junctions through trans-heterophilic interaction with CD155, a vitronectin and poliovirus receptor that localizes to alpha(v)beta3 integrin-containing membrane microdomains.''; PubMedEurope PMCScholia
Ebnet K, Suzuki A, Horikoshi Y, Hirose T, Meyer Zu Brickwedde MK, Ohno S, Vestweber D.; ''The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM).''; PubMedEurope PMCScholia
Sterk LM, Geuijen CA, Oomen LC, Calafat J, Janssen H, Sonnenberg A.; ''The tetraspan molecule CD151, a novel constituent of hemidesmosomes, associates with the integrin alpha6beta4 and may regulate the spatial organization of hemidesmosomes.''; PubMedEurope PMCScholia
Koster J, Geerts D, Favre B, Borradori L, Sonnenberg A.; ''Analysis of the interactions between BP180, BP230, plectin and the integrin alpha6beta4 important for hemidesmosome assembly.''; PubMedEurope PMCScholia
Dougherty GW, Jose C, Gimona M, Cutler ML.; ''The Rsu-1-PINCH1-ILK complex is regulated by Ras activation in tumor cells.''; PubMedEurope PMCScholia
Lemmers C, Médina E, Delgrossi MH, Michel D, Arsanto JP, Le Bivic A.; ''hINADl/PATJ, a homolog of discs lost, interacts with crumbs and localizes to tight junctions in human epithelial cells.''; PubMedEurope PMCScholia
Reymond N, Fabre S, Lecocq E, Adelaïde J, Dubreuil P, Lopez M.; ''Nectin4/PRR4, a new afadin-associated member of the nectin family that trans-interacts with nectin1/PRR1 through V domain interaction.''; PubMedEurope PMCScholia
Ali J, Liao F, Martens E, Muller WA.; ''Vascular endothelial cadherin (VE-cadherin): cloning and role in endothelial cell-cell adhesion.''; PubMedEurope PMCScholia
Fontao L, Favre B, Riou S, Geerts D, Jaunin F, Saurat JH, Green KJ, Sonnenberg A, Borradori L.; ''Interaction of the bullous pemphigoid antigen 1 (BP230) and desmoplakin with intermediate filaments is mediated by distinct sequences within their COOH terminus.''; PubMedEurope PMCScholia
Hülsken J, Birchmeier W, Behrens J.; ''E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton.''; PubMedEurope PMCScholia
Dickson KA, Kang DK, Kwon YS, Kim JC, Leland PA, Kim BM, Chang SI, Raines RT.; ''Ribonuclease inhibitor regulates neovascularization by human angiogenin.''; PubMedEurope PMCScholia
SDK1 and SDK2 are homophilic adhesion molecules. Cells expressing them exhibit a strong preference to interact exclusively with cells expressing the same sidekick form. The N-terminal four Ig domains are arranged in a horseshoe conformation and mediate homophilic adhesion, with Ig1-2 conferring the majority of binding affinity and differential specificity.
SDK1 and SDK2 are homophilic adhesion molecules. Cells expressing them exhibit a strong preference to interact exclusively with cells expressing the same sidekick form. The N-terminal four Ig domains are arranged in a horseshoe conformation and mediate homophilic adhesion, with Ig1-2 conferring the majority of binding affinity and differential specificity.
Cadherins are the major cell adhesion molecules at adherens junctions (AJs). Classical cadherins are Ca2+-dependent, homophilic adhesion molecules that link adjacent cells (Gumbiner, 2005; Halbleib and Nelson, 2006; Pokutta and Weis, 2007). The extracellular domain of classical cadherins consists of five cadherin-type repeats (called "extracellular cadherin" (EC) -domains). In the presence of Ca2+, the monomers form parallel cis-dimers resulting in a rod-like structure (Gumbiner, 2005). The cis-dimers undergo trans homophilic interactions to mediate homotypic cell-cell interactions. The cytoplasmic tails of classical cadherins interact with different proteins (primarily catenins) to regulate cell surface expression levels, linkage to the actin cytoskeleton, and cell signaling. Non-classical cadherins (Atypical cadherins, Proto-cadherins, cadherin-related proteins) have a variable number of cadherin-type repeats, do not associate with catenins, and are not associated with AJs (Halbleib and Nelson, 2006).
The cytoplasmic tails of classical cadherins form a multiprotein complex with alpha-catenin, beta/gamma-catenins and p120 catenin (p120ctn) (Gumbiner, 2005). Beta-catenin and p120ctn directly interact with the cadherin molecule through highly conserved regions in the membrane-distal and membrane-proximal domains, respectively, of the cadherin. The interactions with beta-catenin and p120ctn regulate cadherin localization at cell-cell contacts as well as its adhesive activity (Halbleib and Nelson, 2006). The association of beta-catenin and alpha-catenin probably serves to link the cadherin-catenin complex to the F-actin cytoskeleton through the protein ELPIN (Abe and Takeichi, 2008). Independently of its association with the cadherin-catenin complex, alpha-catenin also regulates the bundling and growth of actin filaments at sites of cell-cell contact formation (Drees et al., 2005; Weis and Nelson, 2006).
Nectins are immunoglobulin-like cell adhesion molecules comprising a family of four members, nectin 1 - 4 (Takai and Nakanishi, 2003). In contrast to classical cadherins which interact only homophilically, nectins undergo trans-homophilic and trans-heterophilic interactions with nectins and nectin-like molecules (Takai et al., 2008b). Nectins cooperate with cadherins in regulating the formation of adherens junctions (AJs) and the strength of cell-cell adhesion. Nectins are linked to the underlying actin cytoskeleton through their interaction with the actin-binding protein Afadin (Takai et al., 2008a). Nectin-based cell–cell adhesions contribute to formation of many types of cell-cell junctions including AJs, tight junctions, and synaptic junctions.
Nectins are Ca(2+)-independent cell adhesion molecules which interact homophilically and heterophilically in trans to form cell-cell adhesions (reviewed in (Sakisaka et al., 2007; Takai et al., 2008). Each nectin first forms homo-cis-dimers and then homo- or hetero-trans-dimers through the extracellular region, causing cell–cell adhesion. The Nectin protein family is made up of four members, nectin-1, -2, -3, and -4, all of which have an extracellular region with three Ig-like loops, a single transmembrane region, and a cytoplasmic tail region.
PAR-3 exists in a ternary complex with aPKC and PAR-6 to form the PAR-aPKC complex (Macara, 2004; Suzuki and Ohno, 2006). This complex is critically involved in the development of Tight Junctions (TJs) from primordial spot-like Adherens Junctions (AJs) (Suzuki et al., 2002). PAR-3 directly interacts with Junctional Adhesion Molecules (JAM)-A, -B, and -C (Ebnet et al., 2001; Ebnet et al., 2004).The interaction with JAM-A might anchor the PAR-aPKC complex to TJs but might also be necessary to recruit the PAR-aPKC complex to primordial spot-like AJs where it becomes activated in response to cell-cell adhesion (reviewed in (Ebnet et al., 2008). The PAR-aPKC complex might also be physically linked to the second polarity protein complex at TJs, the CRB3-Pals1-PATJ complex through a direct interaction between PAR-6 and Pals1 (Hurd et al., 2003).
Claudins are the major cell adhesion molecules in tight junctions and are involved in regulating the paracellular flux of water-soluble molecules between adjacent cells (reviewed in (Furuse and Tsukita, 2006). Claudins create paired strands through homophilic and heterophilic cis and trans interactions. A strand of one cell associates laterally with a strand in the apposing membrane of an adjacent cell creating a paired TJ strand (Tsukita et al., 2001). The TJ strands contain aqueous pores with size and charge selectivity that are permeable to water-soluble molecules. Differences in the barrier properties in epithelia of different tissues have been explained by the expression of a unique set of claudins in a given tissue (Van Itallie and Anderson, 2006). 24 claudins were identified in humans, which allows a large number of possible combinations and specific barrier properties.
The nectin-like (Necl) family comprises five members, called Necl-1 to -5. Necl have an overall organization like that of nectins with three Ig-like domains, a transmembrane region and a cytoplasmic domain. Necls have a greater variety of functions than nectins and are ubiquitously expressed. In contrast to nectins, Necls do not interact with afadin. Transhomodimerization has been described for Necl-1, -2 and -3 but not for Necl-4 and -5. (Sakisaka et al., 2007; Sakisaka and Takai, 2004; Takai et al., 2008).
The CRB3–Pals1–PATJ complex is the second major cell polarity protein complex at Tight Junctions (TJs) (Shin et al., 2006). The integral membrane protein CRB3 localizes to the apical domain of epithelial cells and is concentrated at TJs. CRB3 directly associates with Pals1 which interacts with PATJ, a proteins consisting of 10 PDZ domains. The interaction with CRB3 might recruit the Pals1-PATJ complex to TJs (Lemmers et al., 2002; Roh et al., 2003). Although its precise functions of the individual components have not been established, the complex is required for TJ formation, in part through the stabilization of apical and lateral components of tight junctions (Michel et al., 2005; Shin et al., 2005).
PARVB interacts with the actin cross-linking protein Alpha-actinin (Yamaji et al. 2004). The ILK-PARVB complex may serve as an integrin-anchoring site for alpha-actinin and thereby mediate integrin signaling to alpha-actinin, which has been shown to play an important role in actin polymerization at focal adhesions (Yamaji et al., 2004).
The Ras suppressor, Rsu-1, interacts with the LIM 5 domain of PINCH1 (but not PINCH2) and may inhibit cell migration by stabilizing the Pinch-ILK-parvin adhesion complex (Dougherty et al., 2008; Kadrmas et al., 2004).
Migfilin functions in cell shape modulation regulating filamin-mediated cross-linking and stabilization of actin filaments. Migfilin is recruited to cell–Extra Cellular Matrix adhesion sites in a variety of fibroblasts, epithelial, and endothelial cells by interaction with Mig-2 (Tu et al., 2003).
Migfilin associates with actin filaments as a result of its interaction with filamin (Tu et al., 2003). Migfilin associates with actin filaments and loss of migfilin decreases the level of F-actin suggesting that, in addition to providing an anchoring site for actin filaments at cell-ECM adhesions, migfilin also functions in the regulation of filamin-mediated cross-linking and stabilization of actin filaments (Tu et al., 2003).
The actin-binding domain of plectin interacts with the first pair of FNIII repeats and the N-terminal 35 amino acids of the connecting segment of integrin b4 ( Geerts et al., 1999; Niessen et al., 1997; Koster et al., 2004). This interaction is thought to be the initial step in hemidesmosome (HD) assembly and is critical for the mechanical stability of the HD. This interaction is destabilized when HD disassembly is required, for example, to allow cell migration during wound healing. The Integrin a6b4 also associates extracellularly with laminin-332 (See Koster et al., 2003).
The Rho GTPases, Cdc42 and Rac1, play critical roles in cell migration by integrating cell-substrate adhesion and actin polymerization. PARVB/affixin appears to participate in the activation of Rac and Cdc42 by associating with alpha PIX through its CH1 domain (Mishima et al., 2004; Rosenberger et al., 2005). This activity of PARVB/affixin could promote the polymerization of actin through the activation of downstream effectors of Rac1/Cdc42, including WASP-Arp2/3 and Mena/VASP. Alpha-PIX, ILK and PARVB can be found at the leading edge of spreading cells (Rosenberger et al., 2005 ), and it is likely that activation of Rac1 and Cdc42 at the lamellipodia in some cells is stimulated by interactions of aPIX with PARVB and regulated by interaction of ILK and PARVB (see Sepulveda and Wu, 2005 ).
BP180 interacts with Plectin following the association of Plectin with Integrin b4 (b4) (Koster et al., 2003). It is not clear whether the binding of BP180 to Plectin and b4 occurs sequentially or at the same time as the interaction between BP180 and Laminin?332.
Following the association of BP180 with the forming hemidesmosome, BP230 is recruited through associations with BP180 and a region on beta 4 integrin that includes the C-terminal 21 amino acids of the connecting segment and the second pair of FNIII repeats (Hopkinson et al.,2000).
The Nectin family of Ca2+-independent cell adhesion molecules (CAMs) is comprised of four members, nectin-1, nectin-2, nectin-3, and nectin-4 (reviewed in Sakisaka et al., 2007). Each nectin first forms homophilic cis-dimers and then forms homophilic or heterophilic trans-dimers involved in cell–cell adhesion. Heterophilic trans-interactions are stronger than homophilic trans-interactions.
CD151 interacts with the extracellular domain of the integrin alpha 6 subunit. CD151 is thought to play a role in the formation and stability of hemidesmosomes by providing a framework for the spatial organization of the hemidesmosomal components (Sterk et al., 2000).
BP180 interacts with Plectin following the association of Plectin with Integrin b4 (b4) (Koster et al., 2003). It is not clear whether the binding of BP180 to Plectin and b4 occurs sequentially or at the same time as the interaction between BP180 and Laminin?332.
The focal adhesion protein alpha-parvin, interacts with paxillin, through the C-terminal CH-containing fragment of the alpha-parvin and paxillin LD motif (Wang et al., 2008; Lorenz et al., 2008). This interaction likely contributes to the localization of the PINCH-ILK-parvin complexes to focal adhesions.
Migfilin interacts with VASP and regulates VASP localization to cell-matrix adhesions (Zhang et al., 2006). Interaction between migfilin and VASP is critical for migfilin-mediated regulation of cell migration (Zhang et al., 2006).
The association of PARVA with TESK1 appears to suppress cell spreading (Lalonde et al. 2005). TESK1 can phosphorylate cofilin and promote F-actin polymerization and cell spreading (Tsumura et al., 2005 ; Toshima et al., 2001; Leeksma et al., 2002). PARVA associates with testicular protein kinase 1 (TESK1) and inhibits its activity (Lalonde et al. 2005).
The PINCH-ILK-parvin complex (Tu et al., 2001; Zhang et al., 2002; Li et al., 1999) localizes to focal adhesions and plays a critical role in the regulation of cell adhesion, cell shape modulation, motility and ECM deposition (Velyvis et al., 2001; Braun et al, 2003). ILK binds PINCH through its N-terminal domain and binds PARVA or PARVB through its C-terminal domain, resulting in formation of the ternary PINCH-ILK-parvin complex (Tu et al., 2001). These complexes form before they are localized to integrin-rich adhesion sites (Zhang et al., 2002). Formation of the ILK-PINCH-parvin complexes stabilizes these proteins by protecting them from degradation by the proteasome (Fukuda et al., 2003).
Angiogenin (ANG) binds to F-actin on the surface of endothelial cells. Once bound, ANG is endocytosed and translocated to the nucleus where it stimulates ribosomal RNA syntheses which induce vascularisation of normal and malignant tissues (Dickson et al. 2009). Defects in ANG can cause amyotrophic lateral sclerosis 9 (ALS9; MIM:611895), a fatal progressive neurodegenerative disorder characterised by the preferential loss of motor neurons in the brain stem, motor cortex and spinal cord, resulting in paralysis and respiratory failure between 3 to 5 years of onset of symptoms (Padhi et al. 2014).
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alpha 6:beta
4:Plectin:BP180:Laminin-322 complex6:beta 4:Plectin
complexAnnotated Interactions
alpha 6:beta
4:Plectin:BP180:Laminin-322 complexalpha 6:beta
4:Plectin:BP180:Laminin-322 complex6:beta 4:Plectin
complex6:beta 4:Plectin
complex