Structural plasticity of actin-spectrin membrane skeleton and functional role of actin and spectrin in axon degeneration

Guiping Wang, David J. Simon, Zhuhao Wu, Deanna M. Belsky, Evan Heller, Melanie K. O’Rourke, Nicholas T. Hertz, Henrik Molina, Guisheng Zhong, Marc Tessier-Lavigne, Xiaowei Zhuang

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Axon degeneration sculpts neuronal connectivity patterns during development and is an early hallmark of several adult-onset neurodegenerative disorders. Substantial progress has been made in identifying effector mechanisms driving axon fragmentation, but less is known about the upstream signaling pathways that initiate this process. Here, we investigate the behavior of the actin-spectrin-based Membrane-associated Periodic Skeleton (MPS), and effects of actin and spectrin manipulations in sensory axon degeneration. We show that trophic deprivation (TD) of mouse sensory neurons causes a rapid disassembly of the axonal MPS, which occurs prior to protein loss and independently of caspase activation. Actin destabilization initiates TD-related retrograde signaling needed for degeneration; actin stabilization prevents MPS disassembly and retrograde signaling during TD. Depletion of bII-spectrin, a key component of the MPS, suppresses retrograde signaling and protects axons against degeneration. These data demonstrate structural plasticity of the MPS and suggest its potential role in early steps of axon degeneration.

Original languageEnglish
Article numbere38730
JournaleLife
Volume8
DOIs
StatePublished - May 2019
Externally publishedYes

Fingerprint

Dive into the research topics of 'Structural plasticity of actin-spectrin membrane skeleton and functional role of actin and spectrin in axon degeneration'. Together they form a unique fingerprint.

Cite this