This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shemesh, T. Articles by Kozlov, M. M. Search for Related Content PubMed PubMed Citation Articles by Shemesh, T. Articles by Kozlov, M. M.

Prefission Constriction of Golgi Tubular Carriers Driven by Local Lipid Metabolism: A Theoretical Model

Tom Shemesh ^*, Alberto Luini , Vivek Malhotra , Koert N. J. Burger  and Michael M. Kozlov ^*

^* Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Cell Biology and Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Santa Maria Imbaro (Chieti) Italy; Cell and Developmental Biology Department, Division of Biology, University of California at San Diego, La Jolla, California; and Department of Molecular Cell Biology, Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands

Correspondence: Address reprint requests to Michael M. Kozlov, Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. Tel.: 972-3-640-7863; Fax: 972-3-640-9113; E-mail: michk{at}post.tau.ac.il.

Membrane transport within mammalian cells is mediated by small vesicular as well as large pleiomorphic transport carriers (TCs). A major step in the formation of TCs is the creation and subsequent narrowing of a membrane neck connecting the emerging carrier with the initial membrane. In the case of small vesicular TCs, neck formation may be directly induced by the coat proteins that cover the emerging vesicle. However, the mechanism underlying the creation and narrowing of a membrane neck in the generation of large TCs remains unknown. We present a theoretical model for neck formation based on the elastic model of membranes. Our calculations suggest a lipid-driven mechanism with a central role for diacylglycerol (DAG). The model is applied to a well-characterized in vitro system that reconstitutes TC formation from the Golgi complex, namely the pearling and fission of Golgi tubules induced by CtBP/BARS, a protein that catalyzes the conversion of lysophosphatidic acid into phosphatidic acid. In view of the importance of a PA-DAG cycle in the formation of Golgi TCs, we assume that the newly formed phosphatidic acid undergoes rapid dephosphorylation into DAG. DAG possesses a unique molecular shape characterized by an extremely large negative spontaneous curvature, and it redistributes rapidly between the membrane monolayers and along the membrane surface. Coupling between local membrane curvature and local lipid composition results, by mutual enhancement, in constrictions of the tubule into membrane necks, and a related inhomogeneous lateral partitioning of DAG. Our theoretical model predicts the exact dimensions of the constrictions observed in the pearling Golgi tubules. Moreover, the model is able to explain membrane neck formation by physiologically relevant mole fractions of DAG.

This article has been cited by other articles:

				Y. Tian, C. Pate, A. Andreolotti, L. Wang, E. Tuomanen, K. Boyd, E. Claro, and S. Jackowski Cytokine secretion requires phosphatidylcholine synthesis J. Cell Biol., June 16, 2008; 181(6): 945 - 957. [Abstract] [Full Text] [PDF]

				D. P. Siegel and B. G. Tenchov Influence of the Lamellar Phase Unbinding Energy on the Relative Stability of Lamellar and Inverted Cubic Phases Biophys. J., May 15, 2008; 94(10): 3987 - 3995. [Abstract] [Full Text] [PDF]

				L. O'Hara, G.-S. Han, S. Peak-Chew, N. Grimsey, G. M. Carman, and S. Siniossoglou Control of Phospholipid Synthesis by Phosphorylation of the Yeast Lipin Pah1p/Smp2p Mg2+-dependent Phosphatidate Phosphatase J. Biol. Chem., November 10, 2006; 281(45): 34537 - 34548. [Abstract] [Full Text] [PDF]