Golgi Vesiculation and Lysosome Dispersion in Cells Lacking Cytoplasmic Dynein

doi:10.1083/jcb.141.1.51

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© The Rockefeller University Press, 0021-9525/1998//51 $5.00
The Journal of Cell Biology, Volume 141, Number 1, , 1998 51-59

Regular Articles

Golgi Vesiculation and Lysosome Dispersion in Cells Lacking Cytoplasmic Dynein

A. Harada, Y. Takei, Y. Kanai, Y. Tanaka, S. Nonaka, and N. Hirokawa

Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Tokyo, 113, Japan

Cytoplasmic dynein, a minus end–directed, microtubule-basedmotor protein, is thought to drive the movement of membranousorganelles and chromosomes. It is a massive complex that consistsof multiple polypeptides. Among these polypeptides, the cytoplasmicdynein heavy chain (cDHC) constitutes the major part of thiscomplex. To elucidate the function of cytoplasmic dynein, wehave produced mice lacking cDHC by gene targeting. cDHC^–/–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 interestingphenotypes. First, the Golgi complex became highly vesiculatedand distributed throughout the cytoplasm. Second, endosomesand lysosomes were not concentrated near the nucleus but weredistributed evenly throughout the cytoplasm. Interestingly,the Golgi "fragments" and lysosomes were still found to beattached to microtubules.

These results show that cDHC is essential for the formationand positioning of the Golgi complex. Moreover, cDHC is requiredfor cell proliferation and proper distribution of endosomesand lysosomes. However, molecules other than cDHC might mediateattachment of the Golgi complex and endosomes/lysosomes to microtubules.

1. Abbreviations in this paper: cDHC, cytoplasmic dynein heavychain; dpc, days postcoitum; ES, embryonic stem; ICM, innercell mass; RT, room temperature.

Address all correspondence to N. Hirokawa, Department of CellBiology and Anatomy, Graduate School of Medicine, Universityof Tokyo, Hongo, Bunkyo-ku, Tokyo, 113, Japan. Tel.: 81-3-3812-2111,ext. 3326. Fax: 81-3-5802-8646. E-mail: hirokawa{at}m.u-tokyo.ac.jp

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