Glial βII spectrin contributes to paranode formation and maintenance

RASBAND, MATTHEW N.; YERMAKOV, LEONID M.; GALIANO, MAURICIO R.; ZHANG, CHUANSHENG; SUSUKI, KEIICHIRO; DUPREE, JEFFREY L.; BENUSA, SAVANNAH D.; TSAI, CHANG-RU; CHANG, KAE-JIUN; GRIGGS, RYAN B.; LIU, YANHONG; HUANG, CLAIRE YU-MEI; ZOLLINGER, DANIEL R.

JOURNAL OF NEUROSCIENCE

SOC NEUROSCIENCE

Lugar: Washington; Año: 2018

0270-6474

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. bII spectrin is expressed in diverse cells and is an essential part of the submembranous cytoskeleton. Here, we show that Schwann cell bII spectrin is highly enriched at paranodes. To elucidate the roles of glial bII spectrin, we generated mutant mice lacking bII 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 mutant mice, but not in young adult mutant mice. Electron microscopy confirmed partial loss of transverse bands at the paranodal axoglial junction in the middle-aged mutant mice in both the PNS and CNS. These findings demonstrate that a spectrin-based cytoskeleton in myelinating glia contributes to formation and maintenance of paranodal junctions.