A role of peripheral myelin protein 2 in lipid homeostasis of myelinating Schwann cells.
Peripheral myelin protein 2 (Pmp2, P2 or Fabp8), a member of the fatty acid binding protein family, was originally described together with myelin basic protein (Mbp or P1) and myelin protein zero (Mpz or P0) as one of the most abundant myelin proteins in the peripheral nervous system (PNS). Although Pmp2 is predominantly expressed in myelinated Schwann cells, its role in glia is currently unknown. To study its function in PNS biology, we have generated a complete Pmp2 knockout mouse (Pmp2(-/-) ). Comprehensive characterization of Pmp2(-/-) mice revealed a temporary reduction in their motor nerve conduction velocity (MNCV). While this change was not accompanied by any defects in general myelin structure, we detected transitory alterations in the myelin lipid profile of Pmp2(-/-) mice. It was previously proposed that Pmp2 and Mbp have comparable functions in the PNS suggesting that the presence of Mbp can partially mask the Pmp2(-/-) phenotype. Indeed, we found that Mbp lacking Shi(-/-) mice, similar to Pmp2(-/-) animals, have preserved myelin structure and reduced MNCV, but this phenotype was not aggravated in Pmp2(-/-) /Shi(-/-) mutants indicating that Pmp2 and Mbp do not substitute each other's functions in the PNS. These data, together with our observation that Pmp2 binds and transports fatty acids to membranes, uncover a role for Pmp2 in lipid homeostasis of myelinating Schwann cells.
Department of Medical Genetics, University of Lausanne, Switzerland; Graduate Program in Neurosciences, University of Lausanne, Switzerland.
Jennifer
J
Zenker
Mark
M
Stettner
Salla
S
Ruskamo
Enric
E
Domènech-Estévez
Hasna
H
Baloui
Jean-Jacques
JJ
Médard
Mark H G
MH
Verheijen
Jos F
JF
Brouwers
Petri
P
Kursula
Bernd C
BC
Kieseier
Roman
R
Chrast
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D018996:Myelin P2 Protein / Q000235:genetics / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D009431:Neural Conduction; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism*; D012584:Sciatic Nerve / Q000473:pathology / Q000503:physiopathology
D005227:Fatty Acids; C499047:Mbp protein, mouse; D004676:Myelin Basic Protein; D018996:Myelin P2 Protein; C560556:Pmp2 protein, mouse; D012333:RNA, Messenger
Pmp2; fatty acid transport; glia; myelin basic protein; peripheral nervous system