Carboxyl-terminal modulator protein (CTMP) deficiency mitigates denervation-induced skeletal muscle atrophy

Area of Science:

• Muscle physiology and neurobiology
• Molecular mechanisms of muscle atrophy
• Biochemistry of protein regulation

Background:

• Denervated skeletal muscles undergo atrophy due to decreased Akt signaling, leading to reduced protein synthesis and increased expression of atrophy-related genes.
• Carboxyl-terminator modulator protein (CTMP) expression is elevated in atrophic muscles of ALS mice and promotes muscle degeneration.
• Previous research suggests CTMP plays a role in muscle catabolism, but its specific involvement in neurogenic atrophy remains unclear.

Purpose of the Study:

• To investigate the role of CTMP in skeletal muscle atrophy induced by sciatic nerve injury (SNI).
• To determine if CTMP deficiency mitigates neurogenic atrophy and restores Akt signaling.
• To elucidate the molecular pathways through which CTMP influences muscle mass and protein homeostasis.

Main Methods:

• Sciatic nerve injury (SNI) model in wild-type (WT) and CTMP knockout (CTMP-KO) mice.
• Assessment of muscle weight and histological analysis of gastrocnemius muscles.
• Western blot analysis to measure levels of Akt, phosphorylated Akt, GSK3β, S6, 4E-BP1, MuRF-1, and myostatin.

Main Results:

• SNI led to increased CTMP expression in WT denervated muscles.
• CTMP-KO mice exhibited significantly greater gastrocnemius muscle weight compared to WT mice after denervation.
• Denervated CTMP-KO muscles showed enhanced Akt signaling (higher phosphorylation of Akt, GSK3β, S6, and 4E-BP1) and reduced levels of MuRF-1 and myostatin.

Conclusions:

• CTMP is a key mediator of muscle atrophy following denervation.
• CTMP deficiency protects against neurogenic muscle atrophy by preserving Akt signaling and protein synthesis.
• Targeting CTMP may represent a therapeutic strategy for combating muscle wasting diseases.