Abstract
Tetraspanins (or proteins from the transmembrane 4 superfamily, TM4SF) form membrane complexes with integrin receptors and are implicated in integrin-mediated cell migration. Here we characterized cellular localization, structural composition, and signaling properties of α3β1–TM4SF adhesion complexes. Double-immunofluorescence staining showed that various TM4SF proteins, including CD9, CD63, CD81, CD82, and CD151 are colocalized within dot-like structures that are particularly abundant at the cell periphery. Differential extraction in conjunction with chemical cross-linking indicated that the cell surface fraction of α3β1–TM4SF protein complexes may not be directly linked to the cytoskeleton. However, in cells treated with cytochalasin B α3β1–TM4SF protein complexes are relocated into intracellular vesicles suggesting that actin cytoskeleton plays an important role in the distribution of tetraspanins into adhesion structures. Talin and MARCKS are partially codistributed with TM4SF proteins, whereas vinculin is not detected within the tetraspanin-containing adhesion structures. Attachment of serum-starved cells to the immobilized anti-TM4SF mAbs induced dephosphorylation of focal adhesion kinase (FAK). On the other hand, clustering of tetraspanins in cells attached to collagen enhanced tyrosine phosphorylation of FAK. Furthermore, ectopic expression of CD9 in fibrosarcoma cells affected adhesion-induced tyrosine phosphorylation of FAK, that correlated with the reorganization of the cortical actin cytoskeleton. These results show that tetraspanins can modulate integrin signaling, and point to a mechanism by which TM4SF proteins regulate cell motility.
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Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 12:45 p.m.) |
Deposited | 2 years, 1 month ago (July 28, 2023, 9:21 p.m.) |
Indexed | 2 months ago (July 1, 2025, 1:24 p.m.) |
Issued | 26 years, 1 month ago (July 26, 1999) |
Published | 26 years, 1 month ago (July 26, 1999) |
Published Online | 26 years, 1 month ago (July 26, 1999) |
Published Print | 26 years, 1 month ago (July 26, 1999) |
@article{Berditchevski_1999, title={Characterization of Integrin–Tetraspanin Adhesion Complexes}, volume={146}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.146.2.477}, DOI={10.1083/jcb.146.2.477}, number={2}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Berditchevski, Fedor and Odintsova, Elena}, year={1999}, month=jul, pages={477–492} }