Apoptotic cleavage of cytoplasmic dynein intermediate chain and p150(Glued) stops dynein-dependent membrane motility.
Cytoplasmic dynein is the major minus end-directed microtubule motor in animal cells, and associates with many of its cargoes in conjunction with the dynactin complex. Interaction between cytoplasmic dynein and dynactin is mediated by the binding of cytoplasmic dynein intermediate chains (CD-IC) to the dynactin subunit, p150(Glued). We have found that both CD-IC and p150(Glued) are cleaved by caspases during apoptosis in cultured mammalian cells and in Xenopus egg extracts. Xenopus CD-IC is rapidly cleaved at a conserved aspartic acid residue adjacent to its NH(2)-terminal p150(Glued) binding domain, resulting in loss of the otherwise intact cytoplasmic dynein complex from membranes. Cleavage of CD-IC and p150(Glued) in apoptotic Xenopus egg extracts causes the cessation of cytoplasmic dynein--driven endoplasmic reticulum movement. Motility of apoptotic membranes is restored by recruitment of intact cytoplasmic dynein and dynactin from control cytosol, or from apoptotic cytosol supplemented with purified cytoplasmic dynein--dynactin, demonstrating the dynamic nature of the association of cytoplasmic dynein and dynactin with their membrane cargo.
Lane
J D
JD
School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
Vergnolle
M A
MA
Woodman
P G
PG
Allan
V J
VJ
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D020169:Caspases / Q000378:metabolism / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D003001:Cloning, Molecular; D000072159:Dynactin Complex; D004398:Dyneins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D046911:Macromolecular Substances; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009865:Oocytes / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000502:physiology; D021122:Protein Subunits; D051381:Rats; D016415:Sequence Alignment; D014981:Xenopus; D029867:Xenopus Proteins
C000606360:DCTN1 protein, human; D000072159:Dynactin Complex; D046911:Macromolecular Substances; D008869:Microtubule-Associated Proteins; D021122:Protein Subunits; D029867:Xenopus Proteins; D020169:Caspases; D004398:Dyneins