ACTL6a coordinates axonal caliber recognition and myelination in the peripheral nerve

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• Schwann cells (SC) in peripheral nerves are responsible for sorting axons by caliber and initiating myelination.
• The precise mechanisms integrating axonal signals with the myelination transcriptional program are not fully understood.

Purpose of the Study:

• To identify key molecular players involved in coordinating axonal caliber recognition with SC myelination.
• To elucidate the role of Actin-like protein 6a (ACTL6a) in this process.

Main Methods:

• Investigated the function of ACTL6a, a component of the SWI/SNF chromatin remodeling complex, in SC.
• Utilized knockout mouse models to assess the in vivo consequences of Actl6a deficiency.
• Examined nuclear ACTL6A levels in SC in response to different axon calibers.

Main Results:

• Increased nuclear ACTL6A in SC upon contact with large caliber axons or nanofibers.
• ACTL6A promotes myelination by facilitating the eviction of repressive histone marks.
• Actl6a knockout mice exhibit defective radial sorting, hypo-myelination of large axons, and aberrant myelination of small axons.
• These defects lead to a discernible motor phenotype.

Conclusions:

• ACTL6A is critical for integrating axonal caliber information with the myelination transcriptional program in peripheral nerves.
• ACTL6A acts as a key regulator, ensuring proper myelination of axons based on their size.
• Dysregulation of ACTL6A function leads to peripheral nerve defects and motor impairments.