
Charles M. Mansbach, II, M. D.
Professor of Medicine and Physiology
Basic Science Investigator
The
Mansbach Laboratory
Our laboratory is interested in the intracellular movement of triacylglycerols
(TAG) from their formation in the endoplasmic reticulum (ER) to the cis
Golgi in a specific and intestinally unique transport vesicle, the pre-chylomicron
transport vesicle (PCTV). The exit of pre-chylomicrons from the ER in
PCTV is the rate-limiting step in the normal absorption of dietary lipids
across the intestinal absorptive cell. We have found that the budding
of PCTV from ER membranes is COPII independent but that COPII proteins
are required for PCTV’s fusion with the cis Golgi. An additional
unique aspect of this vesicle is that it uses VAMP7 as its v-SNARE in
Golgi fusion. The small Mr protein, liver-fatty acid binding protein (L-FABP),
is utilized as the initiator of budding of PCTV instead of Sar1 and the
COPII proteins for vesicles that transport newly synthesized proteins
from ER to Golgi in the intestine.
Currently, our laboratory is investigating regulatory aspects of both
the budding and the Golgi fusion process since our prior in vivo physiological
studies have shown that chylomicron output into the lymph can be regulated.
We are also trying to understand the targeting determinants on PCTV for
its docking with the Golgi since more than VAMP7 is required. We use a
variety of cell and molecular biological techniques to perform required
studies and take advantage of unique aspects of intestinal physiology
to achieve our research goals.
Research support:
1. NIH 1 RO1 DK38760 - The Regulation of Intestinal Lipid Transport
P.I.: Charles M. Mansbach, II, M.D.
1/10/97 - 6/30/08; $812,000
2. NIH 1 RO1 DK074565-01 – A Cell Biological Approach to Lipid Absorption
P.I.: Charles M. Mansbach, II, M.D.
5/1/06 – 4/30/11 - $1,250,000
Members
of the Mansbach Lab

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