Distinct recycling of active and inactive ß1 integrins.
Traffic
; 13(4): 610-25, 2012 Apr.
Article
en En
| MEDLINE
| ID: mdl-22222055
Integrin trafficking plays an important role in cellular motility and cytokinesis. Integrins undergo constant endo/exocytic shuttling to facilitate the dynamic regulation of cell adhesion. Integrin activity toward the components of the extracellular matrix is regulated by the ability of these receptors to switch between active and inactive conformations. Several cellular signalling pathways have been described in the regulation of integrin traffic under different conditions. However, the interrelationship between integrin activity conformations and their endocytic fate have remained incompletely understood. Here, we have investigated the endocytic trafficking of active and inactive ß1 integrins in cancer cells. Both conformers are endocytosed in a clathrin- and dynamin-dependent manner. The net endocytosis rate of the active ß1 integrins is higher, whereas endocytosis of the inactive ß1 integrin is counteracted by rapid recycling back to the plasma membrane via an ARF6- and early endosome antigen 1-positive compartment in an Rab4a- and actin-dependent manner. Owing to these distinct trafficking routes, the two receptor pools display divergent subcellular localization. At steady state, the inactive ß1 integrin is mainly on the plasma membrane, whereas the active receptor is predominantly intracellular. These data provide new insights into the endocytic traffic of integrins and imply the possibility of a previously unappreciated crosstalk between pathways regulating integrin activity and traffic.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Integrina beta1
/
Endocitosis
Límite:
Humans
Idioma:
En
Revista:
Traffic
Asunto de la revista:
FISIOLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Finlandia
Pais de publicación:
Reino Unido