Ion Channels in the Lysosome: Opening the Gate to the Cell’s Recycling Center.



Time: 16:00, Jan. 18, 2016
Venue: 143, Life Sciences Building, Tsinghua University
Speaker: Haoxin Xu, Ph.D.

Associate Professor, Department of MCDB, University of Michigan

Host: Dr. Xiaodong Liu


Lysosomes are acidic compartments filled with more than 60 different types of hydrolases. They mediate the degradation of extracellular particles from endocytosis and of intracellular components from autophagy. The digested products are transported out of the lysosome via specific catabolite exporters or via vesicular membrane trafficking. Lysosomes also contain more than 50 membrane proteins and are equipped with the machinery to sense nutrient availability, which determines the distribution, number, size, and activity of lysosomes to control the specificity of cargo flux and timing (the initiation and termination) of degradation. Defects in degradation, export, or trafficking result in lysosomal dysfunction and lysosomal storage diseases (LSDs). Lysosomal channels and transporters mediate ion flux across perimeter membranes to regulate lysosomal ion homeostasis, membrane potential, catabolite export, membrane trafficking, and nutrient sensing. Dysregulation of lysosomal channels underlies the pathogenesis of many LSDs and possibly that of metabolic and common neurodegenerative diseases. In order to study ion channels in the lysosome, we have recently developed a modified patch-clamp technique to directly record lysosomal membranes, and also established a fluorescence imaging method to specifically measure lysosomal Ca(2+) release using lysosome-targeted Genetically-Encoded Ca(2+) Indicators, such as GCaMP3. Using these approaches, we were able to "open" the gate to the "black box" of the cell's recycling center and discovered several novel ion channels in the lysosome. We are currently characterizing these new lysosome channels and investigating their cell biological functions.



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