A novel multiprotein complex is required to generate the prechylomicron transport vesicle from intestinal ER

Shahzad Siddiqi, Umair Saleem, Nada A. Abumrad, Nicholas O. Davidson, Judith Storch, Shadab A. Siddiqi, Charles M. Mansbach

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Dietary lipid absorption is dependent on chylomicron production whose rate-limiting step across the intestinal absorptive cell is the exit of chylomicrons from the endoplasmic reticulum (ER) in its ER-to-Golgi transport vesicle, the prechylomicron transport vesicle (PCTV). This study addresses the composition of the budding complex for PCTV. Immunoprecipitation (IP) studies from rat intestinal ER solubilized in Triton X-100 suggested that vesicle-associated membrane protein 7 (VAMP7), apolipoprotein B48 (apoB48), liver fatty acid-binding protein (L-FABP), CD36, and the COPII proteins were associated on incubation of the ER with cytosol and ATP. This association was confirmed by chromatography of the solubilized ER over Sephacryl S400-HR in which these constituents cochromatographed with an apparent kDa of 630. No multiprotein complex was detected when the ER was chromatographed in the absence of PCTV budding activity (resting ER or PKCζ depletion of ER and cytosol). Treatment of the ER with antiapoB48 or anti-VAMP7 antibodies or using gene disrupted L-FABP or CD36 mice all significantly inhibited PCTV generation. A smaller complex (no COPII proteins) was formed when only rL-FABP was used to bud PCTV.jlr The data support the conclusion that the PCTV budding complex in intestinal ER is composed of VAMP7, apoB48, CD36, and L-FABP, plus the COPII proteins.

Original languageEnglish (US)
Pages (from-to)1918-1928
Number of pages11
JournalJournal of lipid research
Volume51
Issue number7
DOIs
StatePublished - Jul 1 2010

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology
  • Cell Biology

Keywords

  • CD36
  • Chylomicron
  • L-FABP
  • Lipid absorption
  • Vesicle budding complex

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