Titin:A Central Hub for Hypertrophy Signaling and Protein Quality Control
Titin(TTN),the largest protein by molecular weight in humans,extends beyond its roles in providing structural stability to the sarcomere and storing elastic potential energy.It also plays a crucial regulatory role in muscle hypertrophy and protein quality control.The protein complex encompassing the Z-disk,Ⅰ-band,and M-line regions of TTN acts as a mechanosensor,dynamically modulating the transduction of myocellular hypertrophic signaling in response to me-chanical tension.TTN induces skeletal muscle remodeling after exercise,mediating the repair and degradation of damaged TTN through protein protection and quality control mechanisms.Under appropriate mechanical stimulation,the TTN mechanosensory complex is activated,thereby triggering a series of hypertrophic responses.Conversely,following overload exercise,severely damaged TTN promotes its degradation through interactions of T-cap with MDM2,the proximal Ig region with calpain 1,and the N2A and M-line regions with calpain 3,as well as en-gagement of the MuRF1 binding site within the M-line domain.In this article,we delve into the role of the cytoskeletal protein TTN as a central signaling hub for skeletal muscle remodeling.Initially,the basic structure of TTN is elucidated,followed by an in-depth analysis of the mecha-nisms by which different regions contribute to muscle hypertrophy and protein quality control.
titinmolecular springmechanical propertieshypertrophy signalingprotein quali-ty control
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维普
