Helping understand more about SPG2 HSP
The interaction between 2 key proteins in developing and maintaining the myelin sheath around nerves, and how both their separate and combined functions are affected in SPG2 HSP is now better understood.
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 (P0null -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 (Plpnull -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 P0null -mice. To determine the functional relevance of PLP expression in the absence of P0, we generated P0null *Plpnull -double-mutant mice. Compared with either single-mutant, P0null *Plpnull -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 P0null *Plpnull -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.
SOURCE: Glia. 2015 Sep 22. doi: 10.1002/glia.22922. [Epub ahead of print] PMID: 26393339 [PubMed – as supplied by publisher] © 2015 Wiley Periodicals, Inc.
Proteolipid protein modulates preservation of peripheral axons and premature death when myelin protein zero is lacking.
Patzig J1, Kusch K1, Fledrich R1, Eichel MA1, Lüders KA1, Möbius W1,2, Sereda MW1,3, Nave KA1, Martini R4, Werner HB1.
1Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
2Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Göttingen, Germany.
3Department of Clinical Neurophysiology, University Medical Center, Göttingen, Germany.
4Department of Neurology, Developmental Neurobiology, University Hospital, Würzburg, Germany.