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 ani mal cells, and associates with many of its cargoes in conjunction with the dynactin complex. Interaction between cytoplasmic dynein and dynactin is me diated 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(G lued) are cleaved by caspases during apoptosis in cultured mammalian cells and in Xenopus egg extracts. Xenopus CD-IC is rapidly cleaved at a conserve d aspartic acid residue adjacent to its: NH2-terminal p150(Glued) binding d omain, 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 ret iculum movement. Motility of apoptotic membranes is restored by recruitment of intact cytoplasmic dynein and dynactin from control cytosol, or from ap optotic cytosol supplemented with purified cytoplasmic dynein-dynactin, dem onstrating the dynamic nature of the: association of cytoplasmic dynein and dynactin with their membrane cargo.