RRC ID 68660
Author Abe M, Makino A, Murate M, Hullin-Matsuda F, Yanagawa M, Sako Y, Kobayashi T.
Title PMP2/FABP8 induces PI(4,5)P2-dependent transbilayer reorganization of sphingomyelin in the plasma membrane.
Journal Cell Rep
Abstract 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)P2)-binding protein. PMP2 induces the tubulation of model membranes in a PI(4,5)P2-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)P2, inducing membrane tubulation and the subsequent transbilayer movement of lipids.
Volume 37(6)
Pages 109935
Published 2021-11-9
DOI 10.1016/j.celrep.2021.109935
PII S2211-1247(21)01408-X
PMID 34758297
MeSH Animals Biological Transport Cell Membrane / genetics Cell Membrane / metabolism* Charcot-Marie-Tooth Disease / genetics Charcot-Marie-Tooth Disease / metabolism* Dogs HeLa Cells Humans Madin Darby Canine Kidney Cells Mutation Myelin P2 Protein / genetics Myelin P2 Protein / metabolism* Phosphatidylinositol 4,5-Diphosphate / metabolism* Sphingomyelins / metabolism*
IF 8.109
DNA material pET28/His6-PMP2 (RDB19203) pET28/His6-PMP2(I43N) (RDB19204) pET28/His6-PMP2(R127Q) (RDB19205) pET28/His6-FABP3 (RDB19206) pET28/His6-FABP4 (RDB19207) pHalo-NT-Lys (RDB19208) pHalo-PMP2 (RDB19209) pHalo-PMP2(I43N) (RDB19210) pHalo-PLCδ-PH (RDB19211) pTRE-PMP2 (RDB19212) pTRE-TRPV4 (RDB19213) pET28/His6-EGFP-Lact-C2 (RDB19214) pET28/His6-NT-Lys (RDB19215) pDEST/mCherry-synaptojanin (RDB19216) pDEST/AcGFP-synaptojanin (RDB19217) pAcGFP-PMP2 (RDB19218) pTRE-SaSMaseC (RDB19219)