Decoupling of activation and effector binding underlies ARF6 priming of fast endocytic recycling.
Curr Biol
; 21(7): 574-9, 2011 Apr 12.
Article
em En
| MEDLINE
| ID: mdl-21439824
ABSTRACT
The small GTP-binding protein ADP-ribosylation factor 6 (ARF6) controls the endocytic recycling pathway of several plasma membrane receptors. We analyzed the localization and GDP/GTP cycle of GFP-tagged ARF6 by total internal reflection fluorescent microscopy. We found that ARF6-GFP associates with clathrin-coated pits (CCPs) at the plasma membrane in a GTP-dependent manner in a mechanism requiring the adaptor protein complex AP-2. In CCP, GTP-ARF6 mediates the recruitment of the ARF-binding domain of downstream effectors including JNK-interacting proteins 3 and 4 (JIP3 and JIP4) after the burst recruitment of the clathrin uncoating component auxilin. ARF6 does not contribute to receptor-mediated clathrin-dependent endocytosis. In contrast, we found that interaction of ARF6 and JIPs on endocytic vesicles is required for trafficking of the transferrin receptor in the fast, microtubule-dependent endocytic recycling pathway. Our findings unravel a novel mechanism of separation of ARF6 activation and effector function, ensuring that fast recycling may be determined at the level of receptor incorporation into CCPs.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Ribosilação do ADP
/
Vesículas Transportadoras
/
Vesículas Revestidas por Clatrina
/
Proteínas Adaptadoras de Transdução de Sinal
/
Proteínas do Tecido Nervoso
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article