Cleavage of MAGI-1, a tight junction PDZ protein, by caspases is an important step for cell-cell detachment in apoptosis

Apoptosis. 2007 Feb;12(2):343-54. doi: 10.1007/s10495-006-0579-6.

Abstract

MAGI-1, a member of the MAGUK family of proteins, is shown to be rapidly cleaved during Fas-induced apoptosis in mouse 3T3 A31 cells, and in UV irradiation- and staurosporine-induced apoptosis in HaCaT cells. This generates a 97 kDa N-terminal fragment that dissociates from the cell membrane; a process that is largely prevented in the presence of the caspase inhibitor Z-VAD-fmk. In addition, we show that in vitro translated radiolabelled MAGI-1 is efficiently cleaved into 97 kDa and 68 kDa fragments by caspases-3 and -7 at physiological concentrations and mutating the MAGI-1 Asp(761) to Ala completely abolished the caspase-induced cleavage. Moreover, in HaCaT cells overexpressing the MAGI-1 Asp(761)Ala mutant the disruption of cell-cell contacts was delayed during apoptosis, whereas other caspase-dependent processes such as nuclear condensation were not affected, suggesting that cell detachment is parallel to them. Thus, MAGI-1 cleavage appears to be an important step in the disassembly of cell-cell contacts during apoptosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Animals
  • Apoptosis* / drug effects
  • Apoptosis* / radiation effects
  • Cadherins / metabolism
  • Caspases / metabolism*
  • Cell Adhesion Molecules
  • Cell Adhesion Molecules, Neuronal
  • Cell Communication*
  • Guanylate Kinases
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Mice
  • Models, Biological
  • Molecular Sequence Data
  • Protein Processing, Post-Translational* / drug effects
  • Protein Processing, Post-Translational* / radiation effects
  • Protein Transport / drug effects
  • Protein Transport / radiation effects
  • Recombinant Fusion Proteins / metabolism
  • Staurosporine / pharmacology
  • Tight Junctions / drug effects
  • Tight Junctions / metabolism*
  • Tight Junctions / radiation effects
  • Time Factors
  • Ultraviolet Rays
  • fas Receptor / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Cadherins
  • Cell Adhesion Molecules
  • Cell Adhesion Molecules, Neuronal
  • Fas protein, mouse
  • Membrane Proteins
  • Recombinant Fusion Proteins
  • fas Receptor
  • Guanylate Kinases
  • MAGI1 protein, human
  • Magi1 protein, mouse
  • Caspases
  • Staurosporine