Organization of focal adhesion plaques is disrupted by action of the HIV-1 protease.
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.
Max-Planck-Institut für Zellbiologie, Rosenhof, 68526 Ladenburg, Germany. rshoeman@zellbio.mpg.de
Robert L
RL
Shoeman
Roland
R
Hartig
Claudia
C
Hauses
Peter
P
Traub
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005333:Fetus; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism*; D015658:HIV Infections / Q000378:metabolism* / Q000503:physiopathology; D016333:HIV Protease / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins; D009154:Mutation / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism; D016608:Talin / Q000187:drug effects / Q000378:metabolism; D014746:Vimentin / Q000187:drug effects / Q000378:metabolism; D016596:Vinculin / Q000187:drug effects / Q000378:metabolism
D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D016608:Talin; D014746:Vimentin; C026742:plastin; D016596:Vinculin; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496051:Ptk2 protein, mouse; D016333:HIV Protease