Tetraspanins in intercellular adhesion of polarized epithelial cells: spatial and functional relationship to integrins and cadherins.
The subcellular distribution of tetraspanin molecules and their functional relationship with integrins in cell-cell adhesion was studied in detail in different polarized epithelial cell models. CD9, CD81 and CD151 tetraspanins were localized at lateral cell-cell contact sites in a similar distribution to E-cadherin. Interestingly, CD9 was partially localized at the apical microvillae of Madin-Darby canine kidney cells forming multimolecular complexes distinct from those found on the basolateral membrane, suggesting the coexistence of differential tetraspanin webs with different subcellular localization. We found that tetraspanin-associated beta1 integrins at cell-to-cell contacts were in a low-affinity conformational state, and that their localization at intercellular contacts was independent of cadherin expression and adhesion. Furthermore, integrin-tetraspanin complexes were functionally relevant in cell-cell adhesion in a cadherin-independent manner, without requiring a conformational change of the integrin moiety. Nevertheless, the integrin alpha3beta1 was ligand-binding competent and this binding did not disrupt association to tetraspanins. Moreover, Chinese hamster ovary cells treated with anti-tetraspanin mAbs or activatory anti-beta1 integrin mAbs were able to develop tubule-like structures. Together, these data support tetraspanin association as a new regulatory mechanism of integrin function and suggest a role for tetraspanins-integrin complexes in providing the cell with the spatial cues necessary for their proper polarization.
Yáñez-Mó
M
M
Servicio de Inmunología, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain.
Tejedor
R
R
Rousselle
P
P
Sánchez -Madrid
F
F
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002846:Chromatography, Affinity; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D016023:Integrins / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D018613:Microscopy, Confocal; D011485:Protein Binding
D015703:Antigens, CD; D015820:Cadherins; D016023:Integrins; D008565:Membrane Proteins