OSBP-related protein 11 (ORP11) dimerizes with ORP9 and localizes at the Golgi-late endosome interface |
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Authors: | You Zhou Mikko I Mäyränpää Wenbin Zhong Daoguang Yan |
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Institution: | a Minerva Foundation Institute for Medical Research, Biomedicum 2U, and National Institute for Health and Welfare/Public Health Genomics Unit, Biomedicum 1, FI-00290, Helsinki, Finland b Department of Biology, Jinan University, Guangzhou 510632, China c Wihuri Research Institute, FI-00140 Helsinki, and the Department of Forensic Medicine, FI-00014 University of Helsinki, Finland d Institute of Biomedicine/Anatomy, FI-00014 University of Helsinki, Helsinki, Finland |
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Abstract: | We characterize here ORP11, a member of the oxysterol-binding protein family. ORP11 is present at highest levels in human ovary, testis, kidney, liver, stomach, brain, and adipose tissue. Immunohistochemistry demonstrates abundant ORP11 in the epithelial cells of kidney tubules, testicular tubules, caecum, and skin. ORP11 in HEK293 cells resides on Golgi complex and LE, co-localizing with GFP-Rab9, TGN46, GFP-Rab7, and a fluorescent medial-trans-Golgi marker. Under electron microscopic observation, cells overexpressing ORP11 displayed lamellar lipid bodies associated with vacuolar structures or the Golgi complex, indicating a disturbance of lipid trafficking. N-terminal fragment of ORP11 (aa 1-292) localized partially to Golgi, but displayed enhanced localization on Rab7- and Rab9-positive LE, while the C-terminal ligand-binding domain (aa 273-747) was cytosolic, demonstrating that the membrane targeting determinants are N-terminal. Yeast two-hybrid screen revealed interaction of ORP11 with the related ORP9. The interacting region was delineated within aa 98-372 of ORP9 and aa 154-292 of ORP11. Overexpressed ORP9 was able to recruit EGFP-ORP11 to membranes, and ORP9 silencing inhibited ORP11 Golgi association. The results identify ORP11 as an OSBP homologue distributing at the Golgi-LE interface and define the ORP9-ORP11 dimer as a functional unit that may act as an intracellular lipid sensor or transporter. |
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Keywords: | Golgi Late endosome Lipid transport ORP9 ORP11 Oxysterol-binding protein |
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