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J. Biol. Chem., Vol. 280, Issue 14, 13902-13905, April 8, 2005

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Microsomal Triglyceride Transfer Protein Promotes the Secretion of Xenopus laevis Vitellogenin A1^*

Jeremy A. Sellers, Li Hou, Daniel R. Schoenberg¶, Silvia R. Batistuzzo de Medeiros||**, Walter Wahli||, and Gregory S. Shelness

From the Department of Pathology, Wake Forest University School of Medicine Winston-Salem, North Carolina 27157-1040, the ^¶Department of Molecular and Cellular Biochemistry, The Ohio State University College of Medicine, Columbus, Ohio 43210, and the ^||Center for Integrative Genomics, University of Lausanne, CH-10015 Lausanne, Switzerland

Vitellogenins (Vtg) are ancient lipid transport and storage proteins and members of the large lipid transfer protein (LLTP) gene family, which includes insect apolipophorin II/I, apolipoprotein B (apoB), and the microsomal triglyceride transfer protein (MTP). Lipidation of Vtg occurs at its site of synthesis in vertebrate liver, insect fat body, and nematode intestine; however, the mechanism of Vtg lipid acquisition is unknown. To explore whether Vtg biogenesis requires the apoB cofactor and LLTP family member, MTP, Vtg was expressed in COS cells with and without coexpression of the 97-kDa subunit of human MTP. Expression of Vtg alone gave rise to a 220-kDa apoprotein, which was predominantly confined to an intracellular location. Coexpression of Vtg with human MTP enhanced Vtg secretion by 5-fold, without dramatically affecting its intracellular stability. A comparison of wild type and a triglyceride transfer-defective form of MTP revealed that both were capable of promoting Vtg secretion, whereas only wild type MTP could promote the secretion of apoB41 (amino-terminal 41% of apoB). These studies demonstrate that the biogenesis of Vtg is MTP-dependent and that MTP is the likely ancestral member of the LLTP gene family.

Received for publication, January 21, 2005

^* This work was supported in part by National Institutes of Health Grant HL49373 (to G. S. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported as a Predoctoral Fellow by National Institutes of Health Training Grant HL07867. Present address: Division of Natural Sciences, Bluefield College, Bluefield, VA 24605.

^** Present address: Laboratório de Biologia Molecular e Genômica, Centro de Biociências, Universidade Federal do Rio Grande do Norte, Campus Universitário, Lagoa Nova, 59078-970, Natal-RN, Brazil.

To whom correspondence should be addressed. Tel.: 336-716-3282; Fax: 336-716-6279; E-mail: gshelnes{at}wfubmc.edu.

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