Regulation of Endothelial Cell Motility by Complexes of Tetraspan Molecules CD81/TAPA-1 and CD151/PETA-3 with α3β1 Integrin Localized at Endothelial Lateral Junctions

Yáñez-Mó, Marı́a; Alfranca, Arántzazu; Cabañas, Carlos; Marazuela, Mónica; Tejedor, Reyes; Ursa, M A; Ashman, Leonie K.; Landázuri, Manuel O.; Sánchez-Madrid, Francisco

doi:10.1083/jcb.141.3.791

Cited by 257 publications

(170 citation statements)

References 92 publications

(106 reference statements)

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“…Our results focus attention on the CD151 cytoplasmic tail as being important for modulation of cytoskeletal engagements. Notably, CD151 complexes with laminin-binding integrins are present in a variety of tissue locations, including smooth muscle costameres (16) and endothelial cell-cell junctions (18,48). Thus, CD151 modulation of adhesion strengthening could play a key role in force-dependent processes such as muscle contraction and angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…In this regard, only the laminin-binding integrins (␣3␤1, ␣6␤1, ␣6␤4, and ␣7␤1) show strong lateral association with CD151, a transmembrane protein in the tetraspanin family (13)(14)(15)(16). mAb perturbation studies indicate that CD151 modulates integrin-dependent migration, neurite outgrowth, and cell morphology on Matrigel (17)(18)(19)(20). The short C-terminal cytoplasmic domain of CD151 was particularly important for ␣6␤1 integrin-mediated spreading, migration, and cellular cable formation on Matrigel (20).…”

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confidence: 99%

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Tetraspanin CD151 regulates α6β1 integrin adhesion strengthening

Lammerding

Kazarov

Huang

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

157

148

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The tetraspanin CD151 molecule associates specifically with laminin-binding integrins, including ␣6␤1. To probe strength of ␣6␤1-dependent adhesion to laminin-1, defined forces (0 -1.5 nN) were applied to magnetic laminin-coated microbeads bound to NIH 3T3 cells. For NIH 3T3 cells bearing wild-type CD151, adhesion strengthening was observed, as bead detachment became more difficult over time. In contrast, mutant CD151 (with the C-terminal region replaced) showed impaired adhesion strengthening. Static cell adhesion to laminin-1, and detachment of beads coated with fibronectin or anti-␣6 antibody were all unaffected by CD151 mutation. Hence, CD151 plays a key role in selectively strengthening ␣6␤1 integrin-mediated adhesion to laminin-1.A dhesion receptors in the integrin family bind simultaneously to extracellular matrix ligands and to cytoskeletal proteins, thereby transducing external biomechanical stimuli into internal biochemical responses. Biomechanical forces mediated through integrins regulate cell migration, extracellular matrix assembly and remodeling, wound healing, and tissue morphogenesis (1-5). The application of defined forces on direct engagement of specific integrins with fibronectin (6), laminin (7), or antibody to the integrin ␤1 subunit (8) results in strengthening of local cytoskeletal linkages. Also, agents such as thrombin may indirectly induce stimulation of integrin-cytoskeletal stiffness, as measured by using fibronectin-coated magnetic beads (9). Because different extracellular matrix protein ligands trigger distinct integrins, coupled to distinct signaling pathways (10-12), mechanisms for regulating cell adhesion-related events could vary considerably. For example, adenocarcinoma cells adhering to fibronectin preferentially develop stress fibers and focal contacts, whereas the same cells adhering to laminin form lamellipodia (10-12). Such results suggest that laminin-binding and fibronectin-binding integrins could have fundamental mechanistic differences. In this regard, only the laminin-binding integrins (␣3␤1, ␣6␤1, ␣6␤4, and ␣7␤1) show strong lateral association with CD151, a transmembrane protein in the tetraspanin family (13-16). mAb perturbation studies indicate that CD151 modulates integrin-dependent migration, neurite outgrowth, and cell morphology on . The short C-terminal cytoplasmic domain of CD151 was particularly important for ␣6␤1 integrin-mediated spreading, migration, and cellular cable formation on Matrigel (20). Besides CD151, several other members of the tetraspanin protein family (such as CD9, CD81, and CD63) also regulate integrin-dependent cell migration. Although tetraspanin proteins may associate with signaling enzymes and regulate signaling pathways (14, 21-23), the mechanisms whereby they affect cell migration and spreading have not been established.The preponderance of evidence suggests that CD151 and other tetraspanins do not modulate integrin-dependent static cell adhesion (22). Because CD151 strongly influences ␣6␤1 integrin-dependent cellular cable format...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Tetraspanin CD151 regulates α6β1 integrin adhesion strengthening

Lammerding

Kazarov

Huang

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

157

148

View full text Add to dashboard Cite

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“…For example, the CD151 protein serves to link ␣ 3 ␤ 1 to the signaling molecule, phosphatidylinositol 4-kinase (28). Also, antibodies to CD151 inhibited ␣ 3 ␤ 1 -dependent motility of neutrophils (28), and antibodies to both CD151 and ␣ 3 ␤ 1 similarly inhibited the motility of endothelial cells (30). Possibly, ␣ 3 ␤ 1 ϪCD151Ϫphosphatidylinositol 4-kinase complexes could serve as a functional unit to support cell migration.…”

mentioning

confidence: 99%

Direct Extracellular Contact between Integrin α3β1 and TM4SF Protein CD151

Yauch¹,

Kazarov²,

Desai³

et al. 2000

Journal of Biological Chemistry

181

163

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Previously we established that the ␣ 3 ␤ 1 integrin shows stable, specific, and stoichiometric association with the TM4SF (tetraspannin) protein CD151. Here we used a membrane impermeable cross-linking agent to show a direct association between extracellular domains of ␣ 3 ␤ 1 and CD151. The ␣ 3 ␤ 1 ؊CD151 association site was then mapped using chimeric ␣ 6 /␣ 3 integrins and CD151/NAG2 TM4SF proteins. Complex formation required an extracellular ␣ 3 site (amino acids (aa) 570 -705) not previously known to be involved in specific integrin contacts with other proteins and a region (aa 186 -217) within the large extracellular loop of CD151. Notably, the anti-CD151 monoclonal antibody TS151r binding epitope, previously implicated in ␣ 3 integrin association, was mapped to the same region of CD151 (aa 186 -217). Finally, we demonstrated that both NH 2 -and COOH-terminal domains of CD151 are located on the inside of the plasma membrane, thus confirming a long suspected model of TM4SF protein topology.

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“…The associations of tetraspanins with different integrins have been extensively examined in various cell types (13,(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). In most of these studies to prevent dissociation of the integrin⅐tetraspanin complexes the analysis (e.g.…”

mentioning

confidence: 99%

Analysis of the CD151·α3β1 Integrin and CD151·Tetraspanin Interactions by Mutagenesis

Berditchevski¹,

Gilbert²,

Griffiths³

et al. 2001

Journal of Biological Chemistry

103

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Transmembrane proteins of the tetraspanin superfamily are associated with various integrins and modulate their function. We performed mutagenesis analysis to establish structural requirements for the interaction of CD151 with the ␣ 3 ␤ 1 integrin and with other tetraspanins. Using a panel of CD151/CD9 chimeras and CD151 deletion mutants we show that the minimal region, which confers stable (e.g. Triton X-100-resistant) association of the tetraspanin with ␣ 3 ␤ 1 , maps within the large extracellular loop (LECL) of CD151 (the amino acid sequence between residues Leu 149 and Glu 213 ). Furthermore, the substitution of 11 amino acids (residues 195-205) from this region for a corresponding sequence from CD9 LECL or point mutations of cysteines in the conserved CCG and PXXCC motifs abolish the interaction. The removal of the LECL CD151 does not affect the association of the protein with other tetraspanins (e.g. CD9, CD81, CD63, and wild-type CD151). On the other hand, the mutation of the CCG motif selectively prevents the homotypic CD151⅐CD151 interaction but does not influence the association of the mutagenized CD151 with other tetraspanins. These results demonstrate the differences in structural requirements for the heterotypic and homotypic tetraspanin⅐tetraspanin interactions. Various deletions involving the small extracellular loop and the first three transmembrane domains prevent surface expression of the CD151 mutants but do not affect the CD151⅐␣ 3 ␤ 1 interaction. The CD151 deletion mutants are accumulated in the endoplasmic reticulum and redirected to the lysosomes. The assembly of the CD151⅐␣ 3 ␤ 1 complex occurs early during the integrin biosynthesis and precedes the interaction of CD151 with other tetraspanins. Collectively, these data show that the incorporation of CD151 into the "tetraspanin web" can be controlled at various levels by different regions of the protein.

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Regulation of Endothelial Cell Motility by Complexes of Tetraspan Molecules CD81/TAPA-1 and CD151/PETA-3 with α3β1 Integrin Localized at Endothelial Lateral Junctions

Cited by 257 publications

References 92 publications

Tetraspanin CD151 regulates α6β1 integrin adhesion strengthening

Tetraspanin CD151 regulates α6β1 integrin adhesion strengthening

Direct Extracellular Contact between Integrin α3β1 and TM4SF Protein CD151

Analysis of the CD151·α3β1 Integrin and CD151·Tetraspanin Interactions by Mutagenesis

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