OSBP-related protein 2 (ORP2) : Unraveling its functions in cellular lipid/carbohydrate metabolism, signaling and F-actin regulation

Show full item record



Permalink

http://hdl.handle.net/10138/306573

Citation

Olkkonen , V M , Koponen , A & Arora , A 2019 , ' OSBP-related protein 2 (ORP2) : Unraveling its functions in cellular lipid/carbohydrate metabolism, signaling and F-actin regulation ' , Journal of Steroid Biochemistry and Molecular Biology , vol. 192 , 105298 . https://doi.org/10.1016/j.jsbmb.2019.01.016

Title: OSBP-related protein 2 (ORP2) : Unraveling its functions in cellular lipid/carbohydrate metabolism, signaling and F-actin regulation
Author: Olkkonen, Vesa M.; Koponen, Annika; Arora, Amita
Contributor: University of Helsinki, Medicum
University of Helsinki, Department of Anatomy
University of Helsinki, Medicum
Date: 2019-09
Language: eng
Number of pages: 7
Belongs to series: Journal of Steroid Biochemistry and Molecular Biology
ISSN: 0960-0760
URI: http://hdl.handle.net/10138/306573
Abstract: Oxysterol-binding protein (OSBP)-related proteins (ORPs) constitute a family of intracellular lipid-binding/transport proteins (LTPs) in eukaryotes. They typically have a modular structure comprising a lipid-binding domain and membrane targeting determinants, being thus suited for function at membrane contact sites. Among the mammalian ORPs, ORP2/OSBPL2 is the only member that only exists as a 'short' variant lacking a membrane-targeting pleckstrin homology domain. ORP2 is expressed ubiquitously and has been assigned a multitude of functions. Its OSBP-related domain binds cholesterol, oxysterols, and phosphoinositides, and its overexpression enhances cellular cholesterol efflux. Consistently, the latest observations suggest a function of ORP2 in cholesterol transport to the plasma membrane (PM) in exchange for phosphatidylinositol 4,5-bisphosphate (PI4,5P(2)), with significant impacts on the concentrations of PM cholesterol and PI4,5P(2). On the other hand, ORP2 localizes at the surface of cytoplasmic lipid droplets (LDs) and at endoplasmic-reticulum-LD contact sites, and its depletion modifies cellular triglyceride (TG) metabolism. Study in an adrenocortical cell line further suggested a function of ORP2 in the synthesis of steroid hormones. Our recent knock-out of ORP2 in human hepatoma cells revealed its function in hepatocellular PI3K/Akt signaling, glucose and triglyceride metabolism, as well as in actin cytoskeletal regulation, cell adhesion, migration and proliferation. ORP2 was shown to interact physically with F-actin regulators such as DIAPH1, ARHGAP12, SEPT9 and MLC12, as well as with IQGAP1 and the Cdc37-Hsp90 chaperone complex controlling the activity of Akt. Interestingly, mutations in OSBPL2 encoding ORP2 are associated with autosomal dominant non-syndromic hearing loss, and the protein was found to localize in cochlear hair cell stereocilia. The functions assigned to ORP2 suggest that this protein, in concert with other LTPs, controls the subcellular distribution of cholesterol in various cell types and steroid hormone synthesis in adrenocortical cells. However, it also impacts cellular TG and carbohydrate metabolism and F-actin-dependent functions, revealing a bewildering spectrum of activities.
Subject: Akt
Actin cytoskeleton
Energy metabolism
Cholesterol transport
OSBPL2
Triglyceride
OXYSTEROL-BINDING-PROTEIN
PLASMA-MEMBRANE
LIPID DROPLETS
TRANSPORT
STEROL
CHOLESTEROL
FAMILY
ER
OVEREXPRESSION
BIOSYNTHESIS
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
1_s2.0_S0960076018307696_main.pdf 2.382Mb PDF View/Open
OSBP_related_pr ... and_F_actin_regulation.pdf 738.9Kb PDF View/Open

This item appears in the following Collection(s)

Show full item record