p95-APP1 links membrane transport to Rac-mediated reorganization of actin

Nat Cell Biol. 2000 Aug;2(8):521-30. doi: 10.1038/35019561.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factor 6
  • ADP-Ribosylation Factors / metabolism
  • Actins / metabolism*
  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Biological Transport
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / isolation & purification
  • Carrier Proteins / metabolism*
  • Cell Adhesion
  • Cell Cycle Proteins*
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism*
  • Cell Movement
  • Cells, Cultured
  • Chick Embryo
  • Chromatography, Affinity
  • Cloning, Molecular
  • Cytoskeleton / metabolism*
  • Endosomes / chemistry
  • Endosomes / metabolism
  • Enzyme Activation
  • Fibroblasts
  • Fluorescent Antibody Technique
  • GTPase-Activating Proteins / chemistry
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / isolation & purification
  • GTPase-Activating Proteins / metabolism*
  • Guanosine Triphosphate / metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Molecular Weight
  • Phosphoproteins*
  • Precipitin Tests
  • Protein Binding
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • rac GTP-Binding Proteins / metabolism*

Substances

  • ADP-Ribosylation Factor 6
  • Actins
  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cell Cycle Proteins
  • GIT1 protein, human
  • GTPase-Activating Proteins
  • Phosphoproteins
  • Recombinant Fusion Proteins
  • Guanosine Triphosphate
  • ADP-Ribosylation Factors
  • ARF6 protein, human
  • rac GTP-Binding Proteins

Associated data

  • GENBANK/AF216970

Grants and funding