Differential effects of cytohesins 2 and 3 on beta1 integrin recycling.
ADP-ribosylation actor 6 (ARF6) regulates the endocytosis and recycling of a variety of proteins and also promotes peripheral actin rearrangements and cell motility. ARF6 is activated by a large number of guanine nucleotide exchange factors, which likely regulate ARF6 at different locations and during different processes. In this study we investigate the roles of the cytohesin ADP-ribosylation factor (ARF)-guanine nucleotide exchange factors during the recycling of integrin beta1. Intriguingly, we find that knockdown and overexpression of ARNO/cytohesin 2 and GRP1/cytohesin 3 have opposing effects on cell adhesion and spreading on fibronectin and on cell migration. We find that ARNO/cytohesin 2 is required for integrin beta1 recycling, whereas GRP1/cytohesin 3 is dispensable for this process. This is the first demonstration of unique roles for these proteins.
Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Seung Ja
SJ
Oh
Lorraine C
LC
Santy
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D004285:Dogs; D004705:Endocytosis; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D020690:GTPase-Activating Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000089982:ADP-Ribosylation Factor 6; D005353:Fibronectins; D020690:GTPase-Activating Proteins; D019012:Integrin beta1; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; C102474:cytohesin-2; C040985:phosphatidylinositol receptors; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human