Stimulation-dependent recycling of integrin beta1 regulated by ARF6 and Rab11.
In comparison to the internalization pathways of endocytosis, the recycling pathways are less understood. Even less defined is the process of regulated recycling, as few examples exist and their underlying mechanisms remain to be clarified. In this study, we examine the endocytic recycling of integrin beta1, a process that has been suggested to play an important role during cell motility by mediating the redistribution of integrins to the migrating front. External stimulation regulates the endocytic itinerary of beta1, mainly at an internal compartment that is likely to be a subset of the recycling endosomes. This stimulation-dependent recycling is regulated by ARF6 and Rab11, and also requires the actin cytoskeleton in an ARF6-dependent manner. Consistent with these observations being relevant for cell motility, mutant forms of ARF6 that affect either actin rearrangement or recycling inhibit the motility of a breast cancer cell line.
Powelka
Aimee M
AM
Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Sun
Jianlan
J
Li
Jian
J
Gao
Minggeng
M
Shaw
Leslie M
LM
Sonnenberg
Arnoud
A
Hsu
Victor W
VW
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D015415:Biomarkers; D002465:Cell Movement / Q000502:physiology*; D022081:Cell Surface Extensions / Q000378:metabolism; D015638:Cytochalasin D / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors; D000199:Actins; D000906:Antibodies; D015415:Biomarkers; D015638:Cytochalasin D; D019012:Integrin beta1; D021122:Protein Subunits; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C000715348:ARF6 protein, human