Abstract

A defining characteristic of eukaryotic cells is the presence of intracellular membranes. The most abundant endomembrane system is the endoplasmic reticulum (ER), which participates in a multiplicity of functions, including protein and lipid synthesis, a variety of metabolic reactions and intracellular signaling. The ER extends in all regions of neurons, including the most distal compartments of dendrites and axons. While membranes of the ER are functionally connected to all membranes of the secretory and endocytic pathways via vesicular transport, they only physically fuse with each other and with vesicles involved in retrograde transport from the Golgi complex. However, close appositions between the ER and other membranes mediated by tethering proteins play important roles in cell physiology, and their dysfunctions result in disease, including neurodegeneration. In my talk I will discuss the properties, regulation and functions of proteins that tether the ER to other membranes with emphasis on proteins that mediate lipid exchange between bilayers independently of vesicular transport. I will focus in particular on VPS13A and VPS13C , a new class of lipid transport proteins whose mutations result in neuroacanthocytosis (a Huntington’s disease-like condition) and Parkinson’s disease respectively.