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Glia. 2016 Jan;64(1):155-74. doi: 10.1002/glia.22922. Epub 2015 Sep 22.

Proteolipid protein modulates preservation of peripheral axons and premature death when myelin protein zero is lacking.

Author information

1
Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
2
Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Göttingen, Germany.
3
Department of Clinical Neurophysiology, University Medical Center, Göttingen, Germany.
4
Department of Neurology, Developmental Neurobiology, University Hospital, Würzburg, Germany.

Abstract

Protein zero (P0) is the major structural component of peripheral myelin. Lack of this adhesion protein from Schwann cells causes a severe dysmyelinating neuropathy with secondary axonal degeneration in humans with the neuropathy Dejerine-Sottas syndrome (DSS) and in the corresponding mouse model (P0(null)-mice). In the mammalian CNS, the tetraspan-membrane protein PLP is the major structural myelin constituent and required for the long-term preservation of myelinated axons, which fails in hereditary spastic paraplegia (SPG type-2) and the relevant mouse model (Plp(null)-mice). The Plp-gene is also expressed in Schwann cells but PLP is of very low abundance in normal peripheral myelin; its function has thus remained enigmatic. Here we show that the abundance of PLP but not of other tetraspan myelin proteins is strongly increased in compact peripheral myelin of P0(null)-mice. To determine the functional relevance of PLP expression in the absence of P0, we generated P0(null)*Plp(null)-double-mutant mice. Compared with either single-mutant, P0(null)*Plp(null)-mice display impaired nerve conduction, reduced motor functions, and premature death. At the morphological level, axonal segments were frequently non-myelinated but in a one-to-one relationship with a hypertrophic Schwann cell. Importantly, axonal numbers were reduced in the vital phrenic nerve of P0(null)*Plp(null)-mice. In the absence of P0, thus, PLP also contributes to myelination by Schwann cells and to the preservation of peripheral axons. These data provide a link between the Schwann cell-dependent support of peripheral axons and the oligodendrocyte-dependent support of central axons.

KEYWORDS:

Charcot-Marie-tooth disease; Dejerine-Sottas syndrome; Schwann cell; glia-axonal support; hereditary spastic paraplegia (SPG-2); myelin; neurodegeneration; neuropathy; oligodendrocyte

PMID:
26393339
DOI:
10.1002/glia.22922
[Indexed for MEDLINE]

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