ACTL6a coordinates axonal caliber recognition and myelination in the peripheral nerve

Authors

• Hye-Jin Park, CUNY Advanced Science Research CenterFollow
• Eric Tsai, CUNY Advanced Science Research Center
• Dennis Huang, CUNY Advanced Science Research CenterFollow
• Michael Weaver, SUNY University at Buffalo
• Luciana Frick, SUNY University at Buffalo
• Ace Alcantara, CUNY Graduate Center
• John J. Moran, University of Wisconsin-Madison
• Julia Patzig, CUNY Graduate CenterFollow
• Carmen V. Melendez-Vasquez, CUNY Hunter CollegeFollow
• Gerald R. Crabtree, Stanford University School of Medicine
• M.L. Feltri, SUNY University at Buffalo
• John Svaren, University of Wisconsin - Madison
• Patricia Casaccia, CUNY Advanced Science Research CenterFollow

Document Type

Article

Publication Date

4-15-2022

Abstract

Cells elaborate transcriptional programs in response to external signals. In the peripheral nerves, Schwann cells (SC) sort axons of given caliber and start the process of wrapping their membrane around them. We identify Actin-like protein 6a (ACTL6a), part of SWI/SNF chromatin remodeling complex, as critical for the integration of axonal caliber recognition with the transcriptional program of myelination. Nuclear levels of ACTL6A in SC are increased by contact with large caliber axons or nanofibers, and result in the eviction of repressive histone marks to facilitate myelination. Without Actl6a the SC are unable to coordinate caliber recognition and myelin production. Peripheral nerves in knockout mice display defective radial sorting, hypo-myelination of large caliber axons, and redundant myelin around small caliber axons, resulting in a clinical motor phenotype. Overall, this suggests that ACTL6A is a key component of the machinery integrating external signals for proper myelination of the peripheral nerve.

Comments

This article was originally published in ISCIENCE, available at https://doi.org/10.1016/j.isci.2022.104132

This work is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0)