Work

Ca 2+ , ROS, IL-6, and p38 MAPK signaling loops underlying alterations in myotube formation induced by a severe MH/CCD mutation in RyR1

Year: 2025

Type: article

Abstract: Overactive RyR1 mutant proteins are associated with muscle disease; interestingly, they increase the number of myonuclei when expressed in C2C12 cells. We discovered that this alteration depends on a Ca 2+ /ROS loop, which recruits calpain and calcineurin to stimulate the production of IL-6 and the subsequent autocrine activation of p38. Thus, disease-causing RyR1 mutations require an IL-6 autocrine system to alter myonuclear density. This novel mechanism could be critical to understanding the pathogenesis of congenital myopathies.

Source: American Journal of Physiology-Cell Physiology

DOI: 10.1152/ajpcell.00509.2025

Authors: Maikel Valle-Clara, Guillermo Ávila

Institutions: Instituto Politécnico Nacional, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional

Language: English

Topic: Muscle Physiology and Disorders

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funder: Consejo Nacional de Ciencia y Tecnología