Glial βII Spectrin Contributes to Paranode Formation and Maintenance

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Keiichiro SusukiMatthew N Rasband

Abstract

Action potential conduction along myelinated axons depends on high densities of voltage-gated Na+ channels at the nodes of Ranvier. Flanking each node, paranodal junctions (paranodes) are formed between axons and Schwann cells in the peripheral nervous system (PNS) or oligodendrocytes in the CNS. Paranodal junctions contribute to both node assembly and maintenance. Despite their importance, the molecular mechanisms responsible for paranode assembly and maintenance remain poorly understood. βII spectrin is expressed in diverse cells and is an essential part of the submembranous cytoskeleton. Here, we show that Schwann cell βII spectrin is highly enriched at paranodes. To elucidate the roles of glial βII spectrin, we generated mutant mice lacking βII spectrin in myelinating glial cells by crossing mice with a floxed allele of Sptbn1 with Cnp-Cre mice, and analyzed both male and female mice. Juvenile (4 weeks) and middle-aged (60 weeks) mutant mice showed reduced grip strength and sciatic nerve conduction slowing, whereas no phenotype was observed between 8 and 24 weeks of age. Consistent with these findings, immunofluorescence microscopy revealed disorganized paranodes in the PNS and CNS of both postnatal day 13 and middle-aged m...Continue Reading

Citations

Jun 23, 2019·Experimental Biology and Medicine·Beata MachnickaAleksander F Sikorski
Jun 14, 2019·Frontiers in Cellular Neuroscience·Cheng-Hsin Liu, Matthew Neil Rasband
Nov 27, 2020·Nature Reviews. Neuroscience·Matthew N Rasband, Elior Peles
Apr 14, 2021·American Journal of Medical Genetics. Part a·Jill A RosenfeldBrendan H Lee
Jul 3, 2021·Nature Genetics·Margot A CousinDamaris N Lorenzo
Nov 21, 2021·Journal of Cellular and Molecular Medicine·Xiaohua MaZhigang Miao

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