L-MPZ, a novel isoform of myelin P0, is produced by stop codon readthrough.

Myelin protein zero (P0 or MPZ) is a major myelin protein (∼30 kDa) expressed in the peripheral nervous system (PNS) in terrestrial vertebrates. Several groups have detected a P0-related 36-kDa (or 35-kDa) protein that is expressed in the PNS as an antigen for the serum IgG of patients with neuropathy. The molecular structure and function of this 36-kDa protein are, however, still unknown.

Classical 18.5-and 21.5-kDa isoforms of myelin basic protein inhibit calcium influx into oligodendroglial cells, in contrast to golli isoforms.

The myelin basic protein (MBP) family arises from different transcription start sites of the golli (gene of oligodendrocyte lineage) complex, with further variety generated by differential splicing. The "classical" MBP isoforms are peripheral membrane proteins that facilitate compaction of the mature myelin sheath but also have multiple protein interactions. The early developmental golli isoforms have previously been shown to promote process extension and enhance Ca(2+) influx into primary and immortalized oligodendrocyte cell lines.

Targeted overexpression of a golli-myelin basic protein isoform to oligodendrocytes results in aberrant oligodendrocyte maturation and myelination.

Recently, several in vitro studies have shown that the golli-myelin basic proteins regulate Ca2+ homoeostasis in OPCs (oligodendrocyte precursor cells) and immature OLs (oligodendrocytes), and that a number of the functions of these cells are affected by cellular levels of the golli proteins. To determine the influence of golli in vivo on OL development and myelination, a transgenic mouse was generated in which the golli isoform J37 was overexpressed specifically within OLs and OPCs. The mouse, called JOE (J37-overexpressing), is severely hypomyelinated between birth and postnatal day 50.

Regulation of store-operated and voltage-operated Ca2+ channels in the proliferation and death of oligodendrocyte precursor cells by golli proteins.

OPCs (oligodendrocyte precursor cells) express golli proteins which, through regulation of Ca2+ influx, appear to be important in OPC process extension/retraction and migration. The aim of the present study was to examine further the role of golli in regulating OPC development. The effects of golli ablation and overexpression were examined in primary cultures of OPCs prepared from golli-KO (knockout) and JOE (golli J37-overexpressing) mice.

Golli myelin basic proteins regulate oligodendroglial progenitor cell migration through voltage-gated Ca2+ influx.

Migration of oligodendrocyte progenitor cells (OPCs) from proliferative zones to their final location in the brain is an essential step in nervous system development. Golli proteins, products of the myelin basic protein gene, can modulate voltage-gated Ca(2+) uptake in OPCs during process extension and retraction. Given the importance of process extension/retraction on movement, the consequences of golli expression on OPC migration were examined in vivo and in vitro using time-lapse imaging of isolated OPCs and acute brain slice preparations from golli KO and golli J37 overexpressing mice (JOE).

The golli-myelin basic protein negatively regulates signal transduction in T lymphocytes.

Protein kinase C (PKC) plays a critical role in signal transduction controlling T lymphocyte activation. Both positive and negative regulation of signal transduction is needed for proper control of T lymphocyte activation. We have found that a golli product of the myelin basic protein (MBP) gene can serve as a negative regulator of signaling pathways in the T lymphocyte, particularly the PKC pathway.

Embryonic expression of the soma-restricted products of the myelin proteolipid gene in motor neurons and muscle.

In addition to classic proteolipid protein (PLP) and DM20, the mouse myelin proteolipid gene produces the sr-PLP and sr-DM20 proteins. The sr-isoforms are localized to the cell bodies of both oligodendrocytes and neurons. However, they are expressed to a greater extent in neurons than they are in glia.

Identification of a protein that interacts with the golli-myelin basic protein and with nuclear LIM interactor in the nervous system.

The myelin basic protein (MBP) gene encodes the classic MBPs and the golli proteins, which are related structurally to the MBPs but are not components of the myelin sheath. A yeast two-hybrid approach was used to identify molecular partners that interact with the golli proteins. A mouse cDNA was cloned that encoded a protein of 261 amino acids and called golli-interacting protein (GIP).

Expression of soma-restricted proteolipid/DM20 proteins in lymphoid cells.

A new family of the myelin proteolipid protein (PLP/DM20) gene products, srPLP/DM20, has been identified recently in thymus and brain. In the central nervous system, srPLP/DM20 products are not localized in the myelin membrane, unlike their classic PLP/DM20 counterparts. In the immune system, the classic PLP/DM20 products appear to be expressed predominantly in thymic cortical epithelium.

Soma-restricted products of the myelin proteolipid gene are expressed primarily in neurons in the developing mouse nervous system.

The myelin proteolipid gene encodes two sets of proteins, the classic PLP and DM20 and the sr (soma-restricted)-PLP and sr-DM20. Unlike the classic proteolipids, the sr-products are expressed in both neurons and oligodendrocytes (OLs) and are not components of the myelin sheath. In OLs, the sr-isoforms are associated with endosomes and recycling vesicles indicating a possible nonmyelin function for these proteins.

Experimental autoimmune encephalomyelitis relapses are reduced in heterozygous golli MBP knockout mice.

Increased golli MBP (golli) expression has been observed in the peripheral immune system of mice in the relapsing phase of EAE, raising the possibility that golli MBP expression in the periphery may contribute to relapses. Here we describe the generation of golli MBP-deficient mice and a comparison of the clinical course of EAE between heterozygous (golli(+/-)) and wild-type (golli(+/+)) mice. There was no difference between the two groups in incidence of disease, severity of the first episode of disease, or remission after the first episode.

Autoreactive T cells can be protected from tolerance induction through competition by flanking determinants for access to class II MHC.

It is not clear why the N-terminal autoantigenic determinant of myelin basic protein (MBP), Ac1-9, is dominant in the B1O.PL (H-2(u)) mouse, given its weak I-A(u)-MHC binding affinity. Similarly, how do high-affinity T cells specific for this determinant avoid negative selection? Because the MBP:1-9 sequence is embryonically expressed uniquely in the context of Golli-MBP, determinants were sought within the contiguous N-terminal "Golli" region that could out-compete MBP:1-9 for MHC binding, and thereby prevent negative selection of the public response to Ac1-9, shown here to be comprised of a V beta 8.

Expression and properties of the recombinant murine Golli-myelin basic protein isoform J37.

A recombinant form of the murine Golli-myelin basic protein (MBP) isoform J37 (rmJ37) has been expressed in Escherichia coli and isolated to 95% purity via metal chelation and ion exchange chromatography. The protein did not aggregate lipid vesicles containing acidic phospholipids, unlike the 18.5 kDa isoform of MBP.