Myelin proteolipid protein—the first 50 years

doi:10.1016/S1357-2725(01)00136-4

The International Journal of Biochemistry & Cell Biology

Volume 34, Issue 3, March 2002, Pages 211-215

https://doi.org/10.1016/S1357-2725(01)00136-4 Get rights and content

Abstract

Myelin proteolipid protein (PLP), the most abundant protein of central nervous system (CNS) myelin, is a hydrophobic integral membrane protein. Because of its physical properties, which make it difficult to work with, progress towards determining the exact function(s) and disease associations of myelin PLP has been slow. However, recent molecular biology advances have given new life to investigations of PLP, and suggest that it has multiple functions within myelin and is of importance in several neurological disorders.

Introduction

The year 2001 marks the 50th anniversary of the discovery of myelin proteolipid protein (PLP), also referred to as Folch–Lees proteolipid or lipophilin [1]. Proteolipids are ubiquitous membrane lipoproteins that are soluble in organic solvents and insoluble in water. They occur as membrane components in many plant, animal and bacterial cells, but are most abundant in brain white matter, where they constitute >50% of the protein of central nervous system (CNS) myelin. Despite extensive studies over the last 50 years, many properties of myelin PLP have remained elusive. Recent technical advances, however, have added much to our understanding of likely functional roles of PLP in myelin and its role in disease.

Section snippets

Structure

Human myelin PLP is encoded by a 15 kb gene organized into 7 exons and located on the X-chromosome at Xq22. Alternative splicing of the PLP gene gives rise to a minor isoform known as DM20. PLP and DM20 share complete sequence identity, except for a 35 amino acid segment, encoded by the 5′ part of exon 3, that is absent from DM20. The full length gene encodes a 276 amino acid intrinsic membrane protein (Fig. 1) with a molecular mass of 30 kDa and a strongly basic isoelectric point. Despite its

Synthesis and degradation

In the CNS, PLP and DM20 are synthesized by oligodendrocytes on membrane bound polysomes directly as the mature protein, and are transported through the Golgi to the cell surface where they are incorporated into compact myelin. The half-life of PLP in myelin is approximately 90 days. The expression of PLP and DM20 is developmentally regulated, but at all developmental ages they contain the same proportion of covalently-bound fatty acids (3–4%, w/w) [3].

Recently, a new exon of the PLP gene in

Biological function

Numerous functions have been proposed for PLP and DM20 in the CNS (reviewed in [6]), including membrane adhesion and compaction of myelin, formation of the myelin intraperiod line, maturation of oligodendrocytes, involvement in early stages of oligodendrocyte/axon interactions and wrapping of the axon, and maintenance and survival of axons. PLP null mice have oligodendrocytes that can assemble compacted myelin sheaths, but with a condensation of the intraperiod line and decreased physical

Pathologies and metabolic disorders associated with PLP

A large range of mutations involving the PLP gene in humans lead to varying degrees of physical and mental retardation. Diseases resulting from PLP gene abnormalities include Pelizaeus–Merzbacher disease (PMD) and spastic paraplegia type 2 (SPG2) (reviewed in [9]). The most common gene abnormality is duplication of a variable sized section of the gene, which usually leads to PMD at the milder end of the spectrum. In contrast, triplication of the PLP gene leads to a severe early-onset form of

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Molecules in focusMyelin proteolipid protein—the first 50 years

Abstract

Introduction

Section snippets

Structure

Synthesis and degradation

Biological function

Pathologies and metabolic disorders associated with PLP

J. Biol. Chem.

Neuron

Prog. Neurobiol.

Neuron

Neuron

FEBS Lett.

Conserved fatty acid composition of proteolipid protein during brain development and in myelin subfractions

Neurochem. Res.

Identification of a new exon in the myelin proteolipid protein gene encoding novel protein isoforms that are restricted to the somata of oligodendrocytes and neurons

J. Neurosci.

Molecules in focus
Myelin proteolipid protein—the first 50 years