Role of myelin Po protein as a homophilic adhesion molecule

Abstract

Peripheral nervous system myelin is an extension of the Schwann cell's plasma membrane that tightly enwraps axons in many layers and permits nerve impulses to be rapidly conducted. It is not known how these multiple membrane layers are held together in this compact form. Here we present evidence supporting the hypothesis that the extracellular leaflets of myelin are held together by the most abundant protein of myelin of the peripheral nervous system, P0, by homophilic interaction of its extracellular domains. Transfected Chinese hamster ovary cells expressing P0 protein adhere to each other in suspension, to form large aggregates, whereas cells that are identical but which do not express P0 do not. We also show that this aggregation is mediated by homophilic binding between P0-expressing cells and that the apposing plasma membranes of these cells specifically form desmosomes, whereas control transfected cells do not. As the only difference between the two cell populations is the expression of P0, this protein is apparently responsible for the changes in morphology and adhesion in the cells that express it. The idea that P0 is a homophilic adhesion molecule is supported by its inclusion in the immunoglobulin supergene family, all members of which are involved in recognition and/or adhesion.

Influence of ovarian stage on transcript profiles in fathead minnow (Pimephales promelas) ovary tissue

“…It is hypothesized that these cord-like structures or differentiated theca cells may play a role in follicular contraction during ovulation (Jalabert and Szollosi, 1975;Van Nassauw et al, 1991). The large fold-change in mpzl2 transcripts, which codes for an adhesion molecule recognized as one of the most abundant myelin proteins of the peripheral nervous system (Filbin et al, 1990), concurs with the enrichment of functional annotation terms related to neuron morphogenesis and development, even though it was not among the features that mapped to an orthologous gene in DAVID. Thus, the four genes with the largest fold change among classes in the present study have four very different functions which all could be plausibly linked to the dynamic process of oogenesis.…”

Autonomic and respiratory dysfunction in Charcot–Marie–Tooth disease due to Thr124Met mutation in the myelin protein zero gene

“…The extracellular domain of P0 is involved in the compaction of the myelin sheath (Filbin et al, 1990). However, the expression of P0 is not confined to Schwann cells that will myelinate axons, as it has also been detected during development in nonmyelinating glial cells of the peripheral nervous system, such as satellite cells in sympathetic and trigeminal ganglia (Filbin et al, 1990;Sommer and Suter, 1998;Hagedorn et al, 1999). Since P0 is expressed long before the onset of myelination, other functions have been speculated upon.…”

Clinical features and molecular modelling of novel MPZ mutations in demyelinating and axonal neuropathies

“…3 Myelin protein zero acts as a homophilic intercellular adhesion molecule, involved in the formation and maintenance of the intraperiod and major dense lines of compact peripheral myelin. 4 Coherently, when expressed in transfected non-glial cell lines, 5,6 MPZ promotes cellular aggregation, although transgenic mice, lacking MPZ expression, are affected by a severe demyelinating neuropathy with in compact myelin sheaths. 7 Furthermore, a crystallographic study of recombinant ECD crystals 8 predicts that adjacent MPZ molecules interact in cis to form a lattice of homotetramers, which potentially adheres in trans to similar structures on opposing myelin loops.…”