Date of Award

Spring 1-1-2012

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

First Advisor

Gia K. Voeltz

Second Advisor

Greg Odorizzi

Third Advisor

Min Han

Fourth Advisor

Andreas Hoenger

Fifth Advisor

Amy Palmer

Abstract

I have identified Rab10 as an ER specific Rab GTPase that regulates ER structure and dynamics. I show that Rab10 localizes to the ER and to dynamic ER-associated structures that track along microtubules and mark the position of new ER tubule growth. Rab10 depletion or expression of a Rab10 GDP-locked mutant alters ER morphology, resulting in a decrease in ER tubules. I demonstrate that this defect is due to a reduced ability of dynamic ER tubules to grow out and successfully fuse with adjacent ER. Consistent with this function, Rab10 partitions to dynamic ER-associated domains found at the leading edge of almost half of all ER tubule dynamics. Interestingly, this Rab10 domain is highly enriched with at least two ER enzymes that regulate phospholipid synthesis, PI Synthase and CEPT1. Both the formation and function of this Rab10/PIS/CEPT1 dynamic domain is inhibited by expression of the GDP-locked Rab10 mutant. Together, these data demonstrate that Rab10 regulates ER dynamics and further suggest that these dynamics are potentially coupled to phospholipid synthesis.

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