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J. Cell Biol.,
Volume 141, Number 1, April 6, 1998 51-59
Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Tokyo, 113, Japan
Cytoplasmic dynein, a minus end-directed,
microtubule-based motor protein, is thought to drive
the movement of membranous organelles and chromosomes. It is a massive complex that consists of multiple
polypeptides. Among these polypeptides, the cytoplasmic dynein heavy chain (cDHC) constitutes the major
part of this complex. To elucidate the function of cytoplasmic dynein, we have produced mice lacking cDHC
by gene targeting. cDHC These results show that cDHC is essential for the formation and positioning of the Golgi complex. Moreover, cDHC is required for cell proliferation and
proper distribution of endosomes and lysosomes. However, molecules other than cDHC might mediate attachment of the Golgi complex and endosomes/lysosomes to microtubules.
/ embryos were indistinguishable from cDHC+/or cDHC+/+ littermates at the
blastocyst stage. However, no cDHC/ embryos were
found at 8.5 d postcoitum. When cDHC/ blastocysts
were cultured in vitro, they showed interesting phenotypes. First, the Golgi complex became highly vesiculated and distributed throughout the cytoplasm. Second, endosomes and lysosomes were not concentrated
near the nucleus but were distributed evenly throughout the cytoplasm. Interestingly, the Golgi "fragments" and lysosomes were still found to be attached to microtubules.
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