Phosphatidylinositol 3′-kinase blocks CD95 aggregation and caspase-8 cleavage at the death-inducing signaling complex by modulating lateral diffusion of CD95

Arun S. Varadhachary, Michael Edidin, Allison M. Hanlon, Marcus E. Peter, Peter H. Krammer, Padmini Salgame

Research output: Contribution to journalArticle

Abstract

Activation of phosphatidylinositol 3′-kinase (PI 3′-K) after ligation of CD3 protects Th2 cells from CD95-mediated apoptosis. Here we show that protection is achieved by inhibition of the formation of CD95 aggregates and consequent activation of caspase-8. Inhibition of aggregate formation is mediated by changes in the actin cytoskeleton, which in turn inhibit lateral diffusion of CD95, reducing its diffusion coefficient, D, 10-fold. After cytochalasin D treatment of stimulated cells, the lateral diffusion of CD95 increases to the value measured on unstimulated cells, and CD95 molecules aggregate to process caspase-8 and mediate apoptosis. Regulation of functional receptor formation by modulating lateral diffusion is a novel mechanism for controlling receptor activity.

Original languageEnglish (US)
Pages (from-to)6564-6569
Number of pages6
JournalJournal of Immunology
Volume166
Issue number11
DOIs
StatePublished - May 1 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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