Oxysterol-binding protein-related protein (ORP) 6 localizes to the ER and ER-plasma membrane contact sites and is involved in the turnover of PI4P in cerebellar granule neurons

Experimental Cell Research
Shinya MochizukiYasuko Noda

Abstract

Oxysterol-binding protein (OSBP)-related proteins (ORPs) are conserved lipid binding proteins found in organisms ranging from yeast to mammals. Recent findings have indicated that these proteins mainly localize to contact sites of 2 different membranous organelles. ORP6, a member of the ORP subfamily III, is one of the least studied ORPs. Using approaches in molecular cell biology, we attempted to study the characteristics of ORP6 and found that ORP6 is abundantly expressed in mouse cultured neurons. Deconvolution microscopy of cultured cerebellar granular cells revealed that ORP6 is localized to the endoplasmic reticulum (ER) and ER-plasma membrane (PM) contact sites, where it co-localized with extended synaptotagmin2 (E-Syt2), a well-known ER-PM contact site marker. E-Syt2 also co-localized with ORP3, another subfamily III member, and ORP5, a subfamily IV member. However, ORP5 does not distribute to the same ER-PM contact sites as subfamily III members. Also, the co-expression of ORP3 but not ORP5 altered the distribution of ORP6 into the processes of cerebellar neurons. Immunoprecipitation demonstrated binding between the intermediate region of ORP6 and ORP3 or ORP6 itself. Additionally, the localization of ORP6 in the PM de...Continue Reading

Citations

Feb 24, 2020·Current Opinion in Cell Biology·Christopher J Stefan
Mar 9, 2021·Frontiers in Cell and Developmental Biology·Bailey HewlettThierry Galli
Jul 13, 2021·Frontiers in Cell and Developmental Biology·Fubito Nakatsu, Asami Kawasaki

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