Myelin Proteolipid Protein: Function in Myelin Structure Is Distinct from Its Role in Oligodendrocyte Development

Abstract

The myelin proteolipid proteins PLP and DM20 are essential for the compaction of central nervous system myelin and they play an important role in the maturation of the oligodendrocyte. The specific function of the less abundant DM20 isoform is still unknown, but rescue experiments previously indicated that both isoforms are necessary for oligodendrocyte maturation. In vitro experiments have suggested DM20 may assist in the translocation of PLP into the membrane. We tested this hypothesis in vivo, by investigating whether wild-type PLP derived from a transgene could be incorporated into the myelin membrane of Plp mutant rumpshaker mice. We previously demonstrated that expression of the PLP transgene alone in a more severe Plp mutant, jimpy mouse, did not result in PLP incorporation into the myelin. Here we report that there was significantly more PLP in white matter from rumpshaker expressing the PLP transgene than their nontransgenic rumpshaker littermates and that myelin structure was improved. The delay in oligodendrocyte development was not alleviated by expression of the PLP transgene however, supporting an essential role for DM20 in oligodendrocyte maturation.

Proteolipid Promoter Activity Distinguishes Two Populations of NG2-Positive Cells throughout Neonatal Cortical Development

“…In fact, it has been shown that both isoforms, but particularly DM20, are required for oligodendrocyte maturation (Nadon and West, 1998). Our studies, as well as others (Spassky et al, 1998), demonstrate that the plp gene is expressed much earlier in the oligodendrocyte lineage than originally thought (Figs.…”

Aberrant dendrite growth in central nervous system white matter induced by a mutant proteolipid protein transgene

“…These findings are supported by in vitro transfection experiments indicating that DM20 assists in the translocation of PLP to the cell surface (Timsit et al, 1992a;Sinoway et al, 1994;Gow et al, 1994;Thomson et al, 1997). In the rumpshaker Plp mutant mouse, which expresses significant amounts of DM20 on the oligodendrocyte surface, correction of the abnormal myelin structure was achieved by adding wild-type PLP alone by way of a transgene (Nadon and West, 1998). However, normalizing the myelin structure did not correlate with alleviation of the oligodendrocyte developmental block.…”

Molecular biology of myelin

“…5 It is also worth mentioning that DM20 doesn't appear in the same state in the CNS and PNS; in the central nervous system it's part of a membrane, while in the peripheral system it's found in cytoplasm of the cell. 6 In addition, even though PLP and DM20 are major players in stabilizing of myelin sheet, they are actually not essential Fig 1.…”