"SHIP164 is a Lipid Transfer Protein that Coordinates Membrane Traffick" by Patreece H. Suen

Date of Award

Spring 2023

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Cell Biology

First Advisor

Reinisch, Karin

Abstract

A defining feature of cells are membrane bilayers that separate them from their environment and, in eukaryotic cells, delineate intracellular organelles with specialized functions. In eukaryotes, the lipid composition of different organellar membranes varies both in terms of bulk and signaling lipids, lending these membranes different biochemical and biophysical characteristics. Yet most lipids are synthesized in the endoplasmic reticulum (ER), then redistributed asymmetrically from there via mechanisms that remain poorly understood. Lipid redistribution is mediated in part by lipid transport proteins that operate at membrane contact sites, where organelles are closely apposed but do not fuse, moving lipids between their membranes. Our lab and others are characterizing a new family of such proteins, called the VPS13-like proteins (or the repeating beta groove (RBG) domain family), that serve as channels for bulk lipid to flow between organelles, for example to facilitate membrane expansion. For my thesis project, my collaborators and I show that the protein SHIP164 shares structural and lipid transfer properties with this family of proteins and demonstrate that it localizes to early endocytic vesicles and contributes to their growth. Our findings raise the intriguing possibility that protein-mediated bulk lipid transfer could play a role in endosomal trafficking and maturation and support that non-vesicular protein-mediated lipid transfer is much more ubiquitous than previously appreciated.

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