We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
An αll Spectrin-Based Cytoskeleton Protects Large-Diameter Myelinated Axons from Degeneration.
- Authors
Yu-Mei Huang, Claire; Chuansheng Zhang; Zollinger, Daniel R.; Leterrier, Christophe; Rasband, Matthew N.
- Abstract
Axons must withstand mechanical forces, including tension, torsion, and compression. Spectrins and actin form a periodic cytoskeleton proposed to protect axons against these forces. However, because spectrins also participate in assembly of axon initial segments (AISs) and nodes of Ranvier, it is difficult to uncouple their roles in maintaining axon integrity from their functions at AIS and nodes. To overcome this problem and to determine the importance of spectrin cytoskeletons for axon integrity, we generated mice with «II spectrin-deficient peripheral sensory neurons. The axons of these neurons are very long and exposed to the mechanical forces associated with limb movement; most lack an AIS, and some are unmyelinated and have no nodes. We analyzed αll spectrin-deficient mice of both sexes and found that, in myelinated axons, αll spectrin forms a periodic cytoskeleton with βIV and βII spectrin at nodes of Ranvier and paranodes, respectively, but that loss of αll spectrin disrupts this organization. Avil-cre;Sptanf/f mice have reduced numbers of nodes, disrupted paranodal junctions, and mislocalized Kvl K + channels. We show that the density of nodal j3IV spectrin is constant among axons, but the density of nodal αll spectrin increases with axon diameter. Remarkably, A vil-cre;Sptanf/f mice have intact nociception and small-diameter axons, but severe ataxia due to preferential degeneration of large-diameter myelinated axons. Our results suggest that nodal αll spectrin helps resist the mechanical forces experienced by large-diameter axons, and that αll spectrin-dependent cytoskeletons are also required for assembly of nodes of Ranvier.
- Subjects
AXONS; SPECTRIN; CYTOSKELETON; NEURODEGENERATION; NODES of Ranvier; PREVENTION
- Publication
Journal of Neuroscience, 2017, Vol 37, Issue 47, p11323
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.2113-17.2017