[Cell Biology] Endoplasmic Reticulum Membrane Contact Sites, Lipid Transport, and Neurodegeneration

Andrés Guillén-Samander1,2 and Pietro De Camilli1,2 1Departments of Neuroscience and of Cell Biology, Howard Hughes Medical Institute, Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, Connecticut 06520, USA 2Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, Maryland 20815, USA Correspondence: pietro.decamilliyale.edu

The Endoplasmic Reticulum (ER) is an endomembrane system that plays a multiplicity of roles in cell physiology and populates even the most distal cell compartments, including dendritic tips and axon terminals of neurons. Some of its functions are achieved by a cross talk with other intracellular membranous organelles and with the plasma membrane at membrane contacts sites (MCSs). As the ER synthesizes most membrane lipids, lipid exchanges mediated by lipid transfer proteins at MCSs are a particularly important aspect of this cross talk, which synergizes with the cross talk mediated by vesicular transport. Several mutations of genes that encode proteins localized at ER MCSs result in familial neurodegenerative diseases, emphasizing the importance of the normal lipid traffic within cells for a healthy brain. Here, we provide an overview of such diseases, with a specific focus on proteins that directly or indirectly impact lipid transport.

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