Interaction between the cytodomains of the alpha 3 and beta 1 integrin subunits regulates remodelling of adhesion complexes on laminin.
The first step of laminin 1-induced signal transduction is initiated by the formation of alpha 6 beta 1 integrin-specific adhesion complexes. In contrast, on other laminin isoforms the adhesion complexes are alpha 3 beta 1 integrin-specific due to a transdominant regulation of the alpha 6 beta 1 integrin by the alpha 3 beta 1 integrin. To determine the mechanism of this regulation, peptides representing the cytoplasmic domain of the alpha 3 or alpha 6 integrin subunits were microinjected together with recombinant enhanced green fluorescence protein into live fibroblasts. Microinjection of the alpha 3 integrin peptide to laminin 1-adherent cells displaying alpha 6 beta 1 integrin-specific adhesion complexes resulted in the disengagement of the alpha 6 beta 1 integrin, while microinjection of green fluorescence protein alone or in combination with the alpha 6 integrin cytodomain had no effect. Further surface plasmon resonance studies revealed that the cytodomain of the beta 1 integrin subunit interacts with low affinity with the cytoplasmic tail of the alpha 3 integrin subunit, but not with that of several other alpha subunits including alpha 6. These results imply that the cytoplasmic tails of the integrin alpha subunits play a critical role in the regulation of integrin-induced signal transduction. In particular, the intracellular tail of the alpha 3 integrin subunit controls the formation of adhesion complexes in cells adhering to laminins.
Laplantine
E
E
Institut II für Biochemie, Faculty of Medicine, University of Cologne, Germany.
Vallar
L
L
Mann
K
K
Kieffer
N
N
Aumailley
M
M
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D003593:Cytoplasm / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D006801:Humans; D039422:Integrin alpha3; D019012:Integrin beta1 / Q000378:metabolism / Q000502:physiology*; D016023:Integrins / Q000378:metabolism / Q000502:physiology*; D007797:Laminin / Q000378:metabolism* / Q000502:physiology; D008845:Microinjections; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000302:isolation & purification / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D020349:Surface Plasmon Resonance
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D039422:Integrin alpha3; D019012:Integrin beta1; D016023:Integrins; D007797:Laminin; D010446:Peptide Fragments