p95-APP1 links membrane transport to Rac-mediated reorganization of actin.
Motility requires protrusive activity at the cellular edge, where Rho family members regulate actin dynamics. Here we show that p95-APP1 (ArfGAP-putative, Pix-interacting, paxillin-interacting protein 1), a member of the GIT1/PKL family, is part of a complex that interacts with Rac. Wild-type and truncated p95-APP1 induce actin-rich protrusions mediated by Rac and ADP-ribosylation factor 6 (Arf6). Distinct p95-APP1-derived polypeptides have different distributions, indicating that p95-APP1 cycles between the cell surface and endosomes. Our results show that p95-APP1 functionally interacts with Rac and localizes to endosomal compartments, thus identifying p95-APP1 as a molecular link between actin organization, adhesion, and membrane transport during cell motility.
Cell Adhesion Unit - DIBIT - S. Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy.
A
A
Di Cesare
S
S
Paris
C
C
Albertinazzi
S
S
Dariozzi
J
J
Andersen
M
M
Mann
R
R
Longhi
I
I
de Curtis
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002448:Cell Adhesion; D018797:Cell Cycle Proteins; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D002642:Chick Embryo; D002846:Chromatography, Affinity; D003001:Cloning, Molecular; D003599:Cytoskeleton / Q000378:metabolism*; D011992:Endosomes / Q000737:chemistry / Q000378:metabolism; D004789:Enzyme Activation; D005347:Fibroblasts; D005455:Fluorescent Antibody Technique; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010750:Phosphoproteins; D011233:Precipitin Tests; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
D000089982:ADP-Ribosylation Factor 6; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C485647:GIT1 protein, human; D020690:GTPase-Activating Proteins; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D006160:Guanosine Triphosphate; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human; D020744:rac GTP-Binding Proteins