Organization of focal adhesion plaques is disrupted by action of the HIV-1 protease

Cell Biol Int. 2002;26(6):529-39. doi: 10.1006/cbir.2002.0895.

Abstract

Focal adhesion plaques were severely affected in human embryonic fibroblasts permeabilized with digitonin and incubated in buffer containing the human immunodeficiency virus type 1 protease (HIV-1 PR). A mutant HIV-1 PR (3271 HIV-1 PR) had no effect on focal adhesion plaques. Similar effects were seen with cells microinjected with either HIV-1 PR or 3271 HIV-1 PR. Immunoblots of the human embryonic fibroblasts demonstrated that a number of focal adhesion plaque proteins were specifically cleaved by HIV-1 PR. These included fimbrin, focal adhesion plaque kinase (FAK), talin, and, to a lesser extent, filamin, spectrin and fibronectin. Proteins detected by antibodies to beta 4 integrin and alpha 3 integrin were also cleaved by the HIV-1 PR. Control experiments demonstrated that the effect and protein cleavages described are due to action of the HIV-1 PR and not to the action of endogenous host cell proteases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Animals
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology*
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism*
  • Cells, Cultured
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Fetus
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Focal Adhesions / drug effects
  • Focal Adhesions / metabolism*
  • HIV Infections / metabolism*
  • HIV Infections / physiopathology
  • HIV Protease / genetics
  • HIV Protease / metabolism*
  • HIV Protease / pharmacology
  • Humans
  • Membrane Glycoproteins / drug effects
  • Membrane Glycoproteins / metabolism
  • Mice
  • Microfilament Proteins*
  • Mutation / physiology
  • Protein-Tyrosine Kinases / drug effects
  • Protein-Tyrosine Kinases / metabolism
  • Talin / drug effects
  • Talin / metabolism
  • Vimentin / drug effects
  • Vimentin / metabolism
  • Vinculin / drug effects
  • Vinculin / metabolism

Substances

  • Membrane Glycoproteins
  • Microfilament Proteins
  • Talin
  • Vimentin
  • plastin
  • Vinculin
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • PTK2 protein, human
  • Ptk2 protein, mouse
  • HIV Protease