# RGMa Nuclear Localization in Skeletal Muscle Cells Reveals a Novel Role in Cell Viability and Proliferation

## TL;DR

This study discovers that RGMa, a protein in muscle cells, localizes to the nucleus and helps regulate cell survival and growth.

## Contribution

The novel finding is RGMa's nuclear localization and its role in promoting muscle cell viability and proliferation.

## Key findings

- RGMa is localized in the nucleus of skeletal muscle cells, revealed by C-terminal antibody staining.
- Neogenin mediates RGMa's nuclear transport, as shown by its absence in Neogenin-knockdown cells.
- RGMa supports muscle cell viability, proliferation, and myogenic commitment in vitro.

## Abstract

The Repulsive Guidance Molecule a (RGMa) is a multifunctional GPI-anchored protein localized in the sarcolemma and sarcoplasm of the adult skeletal muscle cell. Our research group showed that RGMa overexpression can promote myoblast fusion and induce hypertrophic muscle fibers during in vitro differentiation. Here, we report that RGMa is expressed in primary skeletal muscle cells cultured in vitro, showing a nuclear localization, revealed by immunostaining with an antibody targeting its C-terminal region (C-RGMa). While RGMa was detected in the nuclei, its canonical receptor, Neogenin, was predominantly found in the perinuclear region. Nuclear RGMa was absent in Neogenin-knockdown cells, suggesting that Neogenin mediates its nuclear transport. Functional assays suggested that RGMa promotes primary skeletal muscle cell viability and proliferation and supports their myogenic commitment. These findings reveal a previously unrecognized nuclear function of RGMa–Neogenin signaling and provide new insights into the regulation of skeletal muscle cell behavior in vitro.