Function of the tetraspanin CD151-alpha6beta1 integrin complex during cellular morphogenesis.
Upon plating on basement membrane Matrigel, NIH3T3 cells formed an anastomosing network of cord-like structures, inhibitable by anti-alpha6beta1 integrin antibodies. For NIH3T3 cells transfected with human CD151 protein, the formation of a cord-like network was also inhibitable by anti-CD151 antibodies. Furthermore, CD151 and alpha6beta1 were physically associated within NIH3T3 cells. On removal of the short 8-amino acid C-terminal CD151 tail (by deletion or exchange), exogenous CD151 exerted a dominant negative effect, as it almost completely suppressed alpha6beta1-dependent cell network formation and NIH3T3 cell spreading on laminin-1 (an alpha6beta1 ligand). Importantly, mutant CD151 retained alpha6beta1 association and did not alter alpha6beta1-mediated cell adhesion to Matrigel. In conclusion, the CD151-alpha6beta1 integrin complex acts as a functional unit that markedly influences cellular morphogenesis, with the CD151 tail being of particular importance in determining the "outside-in" functions of alpha6beta1-integrin that follow ligand engagement. Also, antibodies to alpha6beta1 and CD151 inhibited formation of endothelial cell cord-like networks, thus pointing to possible relevance of CD151-alpha6beta1 complexes during angiogenesis.
Zhang
Xin A
XA
Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Kazarov
Alexander R
AR
Yang
Xiuwei
X
Bontrager
Alexa L
AL
Stipp
Christopher S
CS
Hemler
Martin E
ME
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D039121:Integrin alpha6beta1; D019012:Integrin beta1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D018715:Microscopy, Video; D009024:Morphogenesis; D011509:Proteoglycans / Q000378:metabolism; D060185:Tetraspanin 24; D014162:Transfection
D015703:Antigens, CD; C554715:CD151 protein, human; C554716:Cd151 protein, mouse; D004338:Drug Combinations; D039121:Integrin alpha6beta1; D019012:Integrin beta1; D016023:Integrins; D007797:Laminin; D046911:Macromolecular Substances; D011509:Proteoglycans; D060185:Tetraspanin 24; C121346:laminin 1; C059485:matrigel; D003094:Collagen