Details

Autor(en) / Beteiligte

• Park, Hye-Jin
• Tsai, Eric
• Huang, Dennis
• Weaver, Michael
• Frick, Luciana
• Alcantara, Ace
• Moran, John J.
• Patzig, Julia
• Melendez-Vasquez, Carmen V.
• Crabtree, Gerald R.
• Feltri, M.L.
• Svaren, John
• Casaccia, Patrizia

Titel

ACTL6a coordinates axonal caliber recognition and myelination in the peripheral nerve

Ist Teil von

• iScience, 2022-04, Vol.25 (4), p.104132, Article 104132

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. [Display omitted] •ACTL6a levels in Schwann cells respond to stiffness and caliber of PLA nanofibers•ACTL6a integrates axonal caliber recognition signals with Schwann cells transcriptome•ACTL6a null mice have thin myelin on large axons and redundant myelin on small axons•Mice lacking ACTL6a in Schwann cells show severe clinical symptoms Biological sciences; Neuroscience; Molecular neuroscience; Cellular neuroscience