N2A Titin: Signaling Hub and Mechanical Switch in Skeletal Muscle.

Int J Mol Sci

Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ 86011-5640, USA.

Published: June 2020

Since its belated discovery, our understanding of the giant protein titin has grown exponentially from its humble beginning as a sarcomeric scaffold to recent recognition of its critical mechanical and signaling functions in active muscle. One uniquely useful model to unravel titin's functions, muscular dystrophy with myositis (mdm), arose spontaneously in mice as a transposon-like LINE repeat insertion that results in a small deletion in the N2A region of titin. This small deletion profoundly affects hypertrophic signaling and muscle mechanics, thereby providing insights into the function of this specific region and the consequences of its dysfunction. The impact of this mutation is profound, affecting diverse aspects of the phenotype including muscle mechanics, developmental hypertrophy, and thermoregulation. In this review, we explore accumulating evidence that points to the N2A region of titin as a dynamic "switch" that is critical for both mechanical and signaling functions in skeletal muscle. Calcium-dependent binding of N2A titin to actin filaments triggers a cascade of changes in titin that affect mechanical properties such as elastic energy storage and return, as well as hypertrophic signaling. The mdm phenotype also points to the existence of as yet unidentified signaling pathways for muscle hypertrophy and thermoregulation, likely involving titin's PEVK region as well as the N2A signalosome.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312179PMC
http://dx.doi.org/10.3390/ijms21113974DOI Listing

Publication Analysis

Top Keywords

n2a titin
8
skeletal muscle
8
critical mechanical
8
mechanical signaling
8
signaling functions
8
small deletion
8
n2a region
8
region titin
8
hypertrophic signaling
8
muscle mechanics
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!