Precise Spatiotemporal Control of Nodal Na

Document Type

Article

Publication Date

6-3-2020

Keywords

JGM

JAX Source

Neuron 2020 Jun 3; 106(5):806-815.e6

Volume

106

Issue

5

First Page

806

Last Page

815

ISSN

1097-4199

PMID

32209430

DOI

https://doi.org/10.1016/j.neuron.2020.03.001

Abstract

During development of the peripheral nervous system (PNS), Schwann-cell-secreted gliomedin induces the clustering of Na+ channels at the edges of each myelin segment to form nodes of Ranvier. Here we show that bone morphogenetic protein-1 (BMP1)/Tolloid (TLD)-like proteinases confine Na+ channel clustering to these sites by negatively regulating the activity of gliomedin. Eliminating the Bmp1/TLD cleavage site in gliomedin or treating myelinating cultures with a Bmp1/TLD inhibitor results in the formation of numerous ectopic Na+ channel clusters along axons that are devoid of myelin segments. Furthermore, genetic deletion of Bmp1 and Tll1 genes in mice using a Schwann-cell-specific Cre causes ectopic clustering of nodal proteins, premature formation of heminodes around early ensheathing Schwann cells, and altered nerve conduction during development. Our results demonstrate that by inactivating gliomedin, Bmp1/TLD functions as an additional regulatory mechanism to ensure the correct spatial and temporal assembly of PNS nodes of Ranvier.

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