ACTL6a coordinates axonal caliber recognition and myelination in the peripheral nerve
Hye-Jin Park,
Eric Tsai,
Dennis Huang,
Michael Weaver,
Luciana Frick,
Ace Alcantara,
John J. Moran,
Julia Patzig,
Carmen V. Melendez-Vasquez,
Gerald R. Crabtree,
M.L. Feltri,
John Svaren,
Patrizia Casaccia
Affiliations
Hye-Jin Park
Advanced Science Research Center (ASRC) at The Graduate Center of the City University of New York (CUNY), New York, NY 10031, USA
Eric Tsai
Advanced Science Research Center (ASRC) at The Graduate Center of the City University of New York (CUNY), New York, NY 10031, USA; Graduate Program in Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Dennis Huang
Advanced Science Research Center (ASRC) at The Graduate Center of the City University of New York (CUNY), New York, NY 10031, USA; Graduate Program in Biology, Graduate Center of CUNY, New York, NY 10016, USA
Michael Weaver
Hunter James Kelly Research Institute, Departments of Biochemistry and Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA
Luciana Frick
Hunter James Kelly Research Institute, Departments of Biochemistry and Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA
Ace Alcantara
Graduate Program in Biology, Graduate Center of CUNY, New York, NY 10016, USA; Hunter College, Department of Biological Sciences, New York, NY 10065, USA
John J. Moran
Waisman Center and Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53705, USA
Julia Patzig
Advanced Science Research Center (ASRC) at The Graduate Center of the City University of New York (CUNY), New York, NY 10031, USA
Carmen V. Melendez-Vasquez
Graduate Program in Biology, Graduate Center of CUNY, New York, NY 10016, USA; Hunter College, Department of Biological Sciences, New York, NY 10065, USA
Gerald R. Crabtree
Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA
M.L. Feltri
Hunter James Kelly Research Institute, Departments of Biochemistry and Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA
John Svaren
Waisman Center and Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53705, USA
Patrizia Casaccia
Advanced Science Research Center (ASRC) at The Graduate Center of the City University of New York (CUNY), New York, NY 10031, USA; Graduate Program in Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate Program in Biology, Graduate Center of CUNY, New York, NY 10016, USA; Corresponding author
Summary: 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.
