HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Papers In Press, published online ahead of print March 1, 2005
J. Lipid Res., doi:10.1194/jlr.M400374-JLR200

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: M400374-JLR200v1 46/3/412    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Smolenaars, M. M. W. Articles by Van der Horst, D. J. Search for Related Content PubMed PubMed Citation Articles by Smolenaars, M. M. W. Articles by Van der Horst, D. J. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 46, 412-421, March 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Biosynthesis and secretion of insect lipoprotein: involvement of furin in cleavage of the apoB homolog, apolipophorin-II/I

Marcel M. W. Smolenaars^*, Marcelle A. M. Kasperaitis^*, Paul E. Richardson, Kees W. Rodenburg^1,* and Dick J. Van der Horst^*

^* Department of Biochemical Physiology, Faculty of Biology and Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands
Department of Chemistry, Coastal Carolina University, Conway, SC 29528

¹ To whom correspondence should be addressed. e-mail: k.w.rodenburg{at}bio.uu.nl

The biosynthesis of neutral fat-transporting lipoproteins involves the lipidation of their nonexchangeable apolipoprotein. In contrast to its mammalian homolog apolipoprotein B, however, insect apolipophorin-II/I (apoLp-II/I) is cleaved posttranslationally at a consensus substrate sequence for furin, resulting in the appearance of two apolipoproteins in insect lipoprotein. To characterize the cleavage process, a truncated cDNA encoding the N-terminal 38% of Locusta migratoria apoLp-II/I, including the cleavage site, was expressed in insect Sf9 cells. This resulted in the secretion of correctly processed apoLp-II and truncated apoLp-I. The cleavage could be impaired by the furin inhibitor decanoyl-Arg-Val-Lys-Arg-chloromethyl ketone (decRVKRcmk) as well as by mutagenesis of the consensus substrate sequence for furin, as indicated by the secretion of uncleaved apoLp-II/I-38. Treatment of L. migratoria fat body, the physiological site of lipoprotein biosynthesis, with decRVKRcmk similarly resulted in the secretion of uncleaved apoLp-II/I, which was integrated in lipoprotein particles of buoyant density identical to wild-type high density lipophorin (HDLp).

These results show that apoLp-II/I is posttranslationally cleaved by an insect furin and that biosynthesis and secretion of HDLp can occur independent of this processing step. Structure modeling indicates that the cleavage of apoLp-II/I represents a molecular adaptation in homologous apolipoprotein structures. We propose that cleavage enables specific features of insect lipoproteins, such as low density lipoprotein formation, endocytic recycling, and involvement in coagulation.

Abbreviations: apoB, apolipoprotein B; apoLp, apolipophorin; decRVKRcmk, decanoyl-Arg-Val-Lys-Arg-chloromethyl ketone; HDLp, high density lipophorin; LDLp, low density lipophorin; LDLR, low density lipoprotein receptor; LLT, large lipid transfer; MTP, microsomal triglyceride transfer protein; PC, proprotein convertase

Supplementary key words apolipoprotein B • homology modeling • low density lipophorin • insect lipoprotein receptor • lipovitellin • precursor • proprotein convertase • vitellogenin

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. M. W. Smolenaars, A. de Morree, J. Kerver, D. J. Van der Horst, and K. W. Rodenburg Insect lipoprotein biogenesis depends on an amphipathic {beta} cluster in apolipophorin II/I and is stimulated by microsomal triglyceride transfer protein J. Lipid Res., September 1, 2007; 48(9): 1955 - 1965. [Abstract] [Full Text] [PDF]

				M. M. W. Smolenaars, O. Madsen, K. W. Rodenburg, and D. J. Van der Horst Molecular diversity and evolution of the large lipid transfer protein superfamily J. Lipid Res., March 1, 2007; 48(3): 489 - 502. [Abstract] [Full Text] [PDF]

				J. A. Sellers, L. Hou, D. R. Schoenberg, S. R. Batistuzzo de Medeiros, W. Wahli, and G. S. Shelness Microsomal Triglyceride Transfer Protein Promotes the Secretion of Xenopus laevis Vitellogenin A1 J. Biol. Chem., April 8, 2005; 280(14): 13902 - 13905. [Abstract] [Full Text] [PDF]