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Originally published In Press as doi:10.1074/jbc.M209137200 on October 30, 2002

J. Biol. Chem., Vol. 278, Issue 3, 1957-1965, January 17, 2003
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Fragmentation of the Golgi Apparatus
A ROLE FOR beta III SPECTRIN AND SYNTHESIS OF PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE*

Anirban SiddhantaDagger , Andreea RadulescuDagger §, Michael C. Stankewich, Jon S. Morrow, and Dennis ShieldsDagger ||**

From the Department of Dagger  Developmental and Molecular Biology and || Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461 and the  Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520

Phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) synthesis has been implicated in maintaining the function of the Golgi apparatus. Here we demonstrate that the inhibition of PtdIns(4,5)P2 synthesis in vitro in response to primary alcohol treatment and the kinetics of Golgi fragmentation in vivo were very rapid and tightly coupled. Preloading Golgi membranes with short chain phosphatidic acid abrogated the alcohol-mediated inhibition of PtdIns(4,5)P2 synthesis in vitro. We also show that fragmentation of the Golgi apparatus in response to diminished PtdIns(4,5)P2 synthesis correlated with both the phosphorylation of a Golgi form of beta III spectrin, a PtdIns(4,5)P2-interacting protein, and changes in its intracellular redistribution. The data are consistent with a model suggesting that the decreased PtdIns(4,5)P2 synthesis and the phosphorylation state of beta III spectrin modulate the structural integrity of the Golgi apparatus.

* This work was supported by National Institutes of Health Grants DK21860 (to D. S.) and DK38979 and DK43812 (to J. S. M.). Core support was provided by National Institutes of Health Cancer Center Grant P30CA13330 (to D. S.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Supported by National Institutes of Health Training Grant T32 GM07491.

** To whom correspondence should be addressed: Dept. of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Tel.: 718-430-2653; Fax: 718-430-8567; E-mail: shields@aecom.yu.edu.

Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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