Non-myelin-forming perisynaptic schwann cells express protein zero and myelin-associated glycoprotein

Perisynaptic Schwann cells (PSCs) envelop axonal terminals and are physiologically distinct from the nearby myelinating Schwann cells (MSCs), which surround the same innervating motor axons. PSCs have special functions at the neuromuscular synapse, where they detect and can modulate neurotransmitter release. Although PSCs are similar to non-myelinating Schwann cells in that they do not form multiple myelin wrappings around nerve terminals, they do wrap around single nerve terminals. These differences, as well as others, lead us to question whether PSCs are truly of Schwann cell origin. We thus characterized the expression of molecules, classically associated with myelin and Schwann cells, in PSCs at the frog neuromuscular junction. We wondered whether PSCs express the Schwann cell marker protein zero (P(0)) and whether their lack of myelination was related to an absence of myelin-associated glycoprotein (MAG), a protein found in myelinating cells that is considered important in myelination. Instead, we found that PSCs express both P(0) and MAG, and other myelinating glial markers such as galactocerebroside and 2',3'-cyclic nucleotide 3'-phosphodiesterase. In denervated preparations, P(0) and MAG expression persisted, including at newly formed PSC extensions. Because PSCs do not myelinate, it is clear that expression of these proteins alone is not sufficient for myelin formation. It is possible that factors present at synapses may prevent myelination, while P(0) and MAG may mediate adhesion between nerve terminals and the surrounding PSCs. The results indicate that PSCs are of Schwann cell origin.