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Fellow: Catherine Chen
Mentor: Ruth Collins
Contact Information: E-mail: rnc8@cornell.edu - Phone: 607-253-4123
Sponsor: American Heart Association
Grant Number: 0715740T
Title: "The YIP1 Family of Integral Membrane Proteins Function in Maintenance of Tubular Endoplasmic Reticulum Networks"
Annual Direct Cost: $21,000
Project Period: 07/01/07-06/30/08
DESCRIPTION (provided by applicant): The endoplasmic reticulum (ER), which represents a contiguous membrane compartment that extends throughout the entire cell, with subdomains that take on disparate shapes. In Saccharomyces cerevisiae, the perinuclear ER is consisted of sheet-like membranes which enclose the nucleus, and membrane tubules which span the cell. The tubular ER network is a conserved feature of all eukaryotes, and is characterized by 50-100nm tubules joined at 3-way junction points. The degree of morphological similarity of this tubular meshwork suggests that there are evolutionarily conserved machineries which generate and maintain its shape. In cardiomyocytes, the sarcoplasmic reticulum (SR) displays extremely precise placement and shape. The SR closely apposes the transverse tubules (TT), and forms a tubular network underlying the plasma membrane. The SR is the main calcium store within myocytes, and its morphology is crucial to propagating the action potential detected at the SR-TT junction throughout the cell in a synchronous fashion. We have discovered that the YIP1 family protein function is needed to maintain the morphology of peripheral ER tubules in yeast. The YIP1 family is a group of integral membrane proteins with homologs present in all eukaryotic genomes sequenced to date. The YIP1 family was originally identified for their ability to interact with the Rab family of monomeric GTPases in a prenylation dependent manner, and contains four paralogs in yeast, of which YIP1 and YIF1 are the essential members. We have previously found that functional YIP1p is needed for biogenesis of COPII coated vesicles. Here we present data that Yip1p and Yif1p also function in maintenance of proper tubular ER morphology. A common feature which connects vesicle budding with tubular membrane maintenance is their need for highly curved membranes. We hypothesize that these proteins possess intrinsic properties in their unique and conserved hydrophobic domains that allow them to modify the curvature of membrane bilayers. I propose to use cell biological experiments in years, in combination with in vitro tabulation and liposome reconstitution assays to test whether Yip1p and Yif1p do indeed affect membrane curvature. I also plan to experimentally determine the membrane topology of Yip1p to investigate whether Yip1p can alter membrane curvature via the shape of its bilayer-embeded portion.
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