Endoplasmic Reticulum – Plasma Membrane Crosstalk Mediated by the Extended Synaptotagmins
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The endoplasmic reticulum (ER) possesses multiplicity of functions including protein synthesis, membrane lipid biogenesis, and Ca2+ storage and has broad localization throughout the cell. While the ER and most other membranous organelles are highly interconnected via vesicular traffic that relies on membrane budding and fusion reactions, the ER forms direct contacts with virtually all other membranous organelles, including the plasma membrane (PM), without membrane fusion. Growing evidence suggests that these contacts play major roles in cellular physiology, including the regulation of Ca2+ homeostasis and signaling and control of cellular lipid homeostasis. Extended synaptotagmins (E-Syts) are evolutionarily conserved family of ER-anchored proteins that tether the ER to the PM in PM PI(4,5)P2-dependent and cytosolic Ca2+-regulated manner. In addition, E-Syts possess a cytosolically exposed lipid-harboring module that confers the ability to transfer/exchange glycerolipids between the ER and the PM at E-Syts-mediated ER-PM contacts. In this chapter, the functions of ER-PM contacts and their role in non-vesicular lipid transport with special emphasis on the crosstalk between the two bilayers mediated by E-Syts will be discussed.
KeywordsE-Syts SMP domain Ca2+ Non-vesicular lipid transport Lipid transfer proteins
We apologize to all the investigators whose work could not be cited due to space limitations. We thank Pietro De Camilli for helpful suggestions. Work from the authors related to this review has been supported in part by a Nanyang Assistant Professorship grant (L0403050) and a Lee Kong Chian School of Medicine Start-up grant (L0412410), Nanyang Technological University, to Y.S.
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