Structure and expression of proteolipid protein in the peripheral nervous system

Abstract

Proteolipid protein (PLP), the major myelin protein in the central nervous system (CNS), is also made by Schwann cells (SC) in the peripheral nervous system (PNS) but is not incorporated into the SC myelin sheath. We analyzed several PLP cDNA clones isolated from a rat sciatic nerve cDNA library and found that their coding sequences were identical to PLP cDNAs previously isolated from the CNS. In addition, we have discovered an unusual form of PLP message, present in both brain and sciatic nerve RNA, that is likely formed by alternative splicing within the 3' untranslated region of the primary PLP transcript. The absence of PLP from the SC myelin sheath thus cannot be explained by an alteration in its amino acid sequence. Steady-state levels of PLP mRNA in SC cultures treated with the cAMP analogue dibutyryl cAMP (dBcAMP) were not increased, whereas dBcAMP increased steady-state levels of mRNA encoding the major myelin protein, P0. We have also shown that expression of PLP, unlike that of P0, is regulated in SC in vitro at a posttranscriptional level. Finally, the steady-state levels of P0 mRNA are much more dramatically reduced than those of PLP mRNA during Wallerian degeneration of the peripheral nerve. Thus PLP expression in the PNS is probably controlled by different molecular mechanisms from P0, and may not be part of the coordinate program of myelin gene expression. In contrast to its expression in the PNS, transcription of PLP in the CNS is coordinately regulated along with the other myelin protein genes, suggesting there may be differences in the cis-acting elements and transacting factors involved in the regulation of PLP transcription in SC and oligodendrocytes (OC). Consistent with this notion, we have found that most PLP transcripts are initiated at the more proximal of two start sites in the PNS, while in the CNS proportionally more PLP transcripts are initiated from the distal start site. We propose that the proximal site, utilized predominantly in SC, is responsible for maintenance expression of PLP and is not inducible, while the distal site is responsible for the rapid, inducible increase of PLP message during brain development.

Myelin-Associated Oligodendrocytic Basic Protein: Identification of an Encephalitogenic Epitope and Association with Multiple Sclerosis

“…Expression of MOBP outside the CNS has not been observed (23,24). In contrast, the MSassociated autoantigens MBP and PLP both are expressed by oligodendrocytes, but also in the peripheral nervous system (52)(53)(54) as well as by cells in the thymus (55). In agreement with the CNSspecific expression of MOBP, we do not detect mononuclear cell infiltration in peripheral organs or the peripheral nervous system after inoculation of SJL/J mice with the encephalitogenic MOBP peptide pool.…”

Protein Zero Gene Expression Is Regulated by the Glial Transcription Factor Sox10

“…PLP, for instance, is only expressed at low levels in Schwann cells, which constitute the myelinating cells of the peripheral nervous system. Furthermore, PLP is not integrated into Schwann cell myelin (16). In the central nervous system, however, PLP accounts for approximately 40% of total myelin protein, and PLP transcripts are highly abundant in oligodendrocytes, which are the myelinating cells of the central nervous system.…”

Jimpy Mutation Affects Astrocytes: Lengthening of the Cell Cycle in vitro

“…This idea suggests that some product of the DM20/PLP gene is a trophic factor, or is involved in the transfer of trophic factors to ASs. Other functional PLP gene products may remain to be de scribed, since alternative splicing has recently been demonstrated in the 3'-untranslated region of the prim ary PLP transcript [29]. Thus, the key to understanding how the jp mutation effects AS function and metabolism may not involve myelin PLP at all, but may be due to another product of the PLP gene with a completely dif ferent function.…”