PMP2/FABP8 induces PI(4,5)P 2 -dependent transbilayer reorganization of sphingomyelin in the plasma membrane.

Autor: Abe M; Lipid Biology Laboratory, RIKEN, Wako, Saitama 351-0198, Japan; Cellular Informatics Laboratory, RIKEN, Wako, Saitama 351-0198, Japan. Electronic address: abemitsu@riken.jp., Makino A; Lipid Biology Laboratory, RIKEN, Wako, Saitama 351-0198, Japan; Cellular Informatics Laboratory, RIKEN, Wako, Saitama 351-0198, Japan., Murate M; Lipid Biology Laboratory, RIKEN, Wako, Saitama 351-0198, Japan; Cellular Informatics Laboratory, RIKEN, Wako, Saitama 351-0198, Japan; Laboratoire de Bioimagerie et Pathologies, UMR 7021 CNRS, Faculté de Pharmacie, Université de Strasbourg, 67401 Illkirch, France., Hullin-Matsuda F; Lipid Biology Laboratory, RIKEN, Wako, Saitama 351-0198, Japan; Université de Lyon, CarMeN Laboratory, INSERM U1060, INRAE U1397, Université Claude Bernard Lyon 1, 69495 Pierre-Benite, France., Yanagawa M; Cellular Informatics Laboratory, RIKEN, Wako, Saitama 351-0198, Japan., Sako Y; Cellular Informatics Laboratory, RIKEN, Wako, Saitama 351-0198, Japan., Kobayashi T; Lipid Biology Laboratory, RIKEN, Wako, Saitama 351-0198, Japan; Cellular Informatics Laboratory, RIKEN, Wako, Saitama 351-0198, Japan; Laboratoire de Bioimagerie et Pathologies, UMR 7021 CNRS, Faculté de Pharmacie, Université de Strasbourg, 67401 Illkirch, France. Electronic address: toshihide.kobayashi@unistra.fr.
Jazyk: angličtina
Zdroj: Cell reports [Cell Rep] 2021 Nov 09; Vol. 37 (6), pp. 109935.
DOI: 10.1016/j.celrep.2021.109935
Abstrakt: Sphingomyelin (SM) is a mammalian lipid mainly distributed in the outer leaflet of the plasma membrane (PM). We show that peripheral myelin protein 2 (PMP2), a member of the fatty-acid-binding protein (FABP) family, can localize at the PM and controls the transbilayer distribution of SM. Genetic screening with genome-wide small hairpin RNA libraries identifies PMP2 as a protein involved in the transbilayer movement of SM. A biochemical assay demonstrates that PMP2 is a phosphatidylinositol 4,5-bisphosphate (PI(4,5)P 2 )-binding protein. PMP2 induces the tubulation of model membranes in a PI(4,5)P 2 -dependent manner, accompanied by the modification of the transbilayer membrane distribution of lipids. In the PM of PMP2-overexpressing cells, inner-leaflet SM is increased whereas outer-leaflet SM is reduced. PMP2 is a causative protein of Charcot-Marie-Tooth disease (CMT). A mutation in PMP2 associated with CMT increases its affinity for PI(4,5)P 2 , inducing membrane tubulation and the subsequent transbilayer movement of lipids.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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