Item Details

title

THE IMPACT OF MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN ON INTRACELLULAR HEPATIC NEUTRAL LIPID DISTRIBUTION AND TRAFFICKING

author

MacArthur, Philip Scott

abstract

Microsomal triglyceride transfer protein (MTP) is a multifunctional protein necessary for conversion of apolipoprotein B into precursor lipoproteins and bulk triglyceride (TG) movement into the endoplasmic reticulum (ER) for precursor lipoprotein expansion. Invertebrate forms of MTP (e.g. Drosophila; dMTP) are capable of phospholipid (PL) transfer, whereas vertebrate forms (e.g. human; hMTP) engage in PL and TG transfer. We hypothesized that PL transfer is the primordial activity of MTP necessary for precursor lipoprotein particle formation, whereas TG transfer is a vertebrate adaptation necessary for trafficking of TG into the ER for 2nd-step assembly. Hence, we assessed hMTP's ability to promote TG trafficking into the ER of transiently transfected or stable, Dox-inducible, non-hepatic cell lines. In cell lines that expressed hMTP, a 2.5 - 5.0-fold increase in microsomal TG content was observed. The lipid-transfer activity of MTP was necessary for this function as in the presence of a potent MTP inhibitor, BMS-212122, microsomal TG content was similar to mock-transfected cells. To determine if the TG-transfer activity of MTP facilitated TG translocation we compared the TG content of microsomes from hMTP and dMTP expressing cells. Compared to mock-transfected cells, hMTP increased microsomal TG content by ~2.5-fold while cells transfected with dMTP demonstrated no increase in microsomal TG content. These data indicate that MTP promotes TG trafficking into the ER and that the TG-transfer activity of MTP is essential for this function.

subject

ApoB

ER

LLTP

MTP

Triglyceride

VLDL assembly

contributor

Shelness, Gregory S. (committee chair)

Dawson, Paul A. (committee member)

Parks, Griffith D. (committee member)

Parks, John S. (committee member)

Temel, Ryan E. (committee member)

date

2013-06-06T21:19:41Z (accessioned)

2015-06-06T08:30:09Z (available)

2013 (issued)

degree

Molecular Pathology (discipline)

embargo

2015-06-06 (terms)

identifier

http://hdl.handle.net/10339/38589 (uri)

language

en (iso)

publisher

Wake Forest University

type

Dissertation