Regulation of Cell Migration and ß1 Integrin Trafficking by the Endosomal Adaptor GGA3.
Traffic
; 17(6): 670-88, 2016 06.
Article
em En
| MEDLINE
| ID: mdl-26935970
ABSTRACT
The integrin family of cell adhesion receptors link extracellular matrices to intracellular signaling pathways and the actin cytoskeleton; and regulate cell migration, proliferation and survival in normal and diseased tissues. The subcellular location of integrin receptors is critical for their function and deregulated trafficking is implicated in various human diseases. Here we identify a role for Golgi-localized gamma-ear containing Arf-binding protein 3 (GGA3), in regulating trafficking of ß1 integrin. GGA3 knockdown reduces cell surface and total levels of α2, α5 and ß1 integrin subunits, inhibits cell spreading, reduces focal adhesion number, as well as cell migration. In the absence of GGA3, integrins are increasingly retained inside the cell, traffic toward the perinuclear lysosomal compartment and their degradation is enhanced. Integrin traffic and maintenance of integrin levels are dependent on the integrity of the Arf binding site of GGA3. Furthermore, sorting nexin 17 (SNX17), a critical regulator of integrin recycling, becomes mislocalized to enlarged late endosomes upon GGA3 depletion. These data support a model whereby GGA3, through its ability to regulate SNX17 endosomal localization and through interaction with Arf6 diverts integrins from the degradative pathway supporting cell migration.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Movimento Celular
/
Integrina beta1
/
Proteínas Adaptadoras de Transporte Vesicular
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Traffic
Assunto da revista:
FISIOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Canadá