Denervated skeletal muscles show decreased Akt activity and phosphorylation, resulting in
atrophy. Akt inhibits downstream transcription of
atrophy-associated
ubiquitin ligases like muscle ring-finger
protein 1 (MuRF-1). In addition, reduced Akt signaling contributes to aberrant
protein synthesis in muscles. In ALS mice, we recently found that carboxyl-terminator modulator
protein (
CTMP) expression is increased and correlated with reduced Akt signaling in atrophic skeletal muscle.
CTMP has also been implicated in promoting muscle degeneration and catabolism in an in vitro
muscle atrophy model. The present study examined whether sciatic nerve injury (SNI) stimulated
CTMP expression in denervated skeletal muscle during
muscle atrophy. We hypothesized that
CTMP deficiency would reduce neurogenic
atrophy and reverse Akt signaling downregulation. Compared to the unaffected contralateral muscle, wild-type (WT) gastrocnemius muscle had a significant increase in
CTMP (p < 0.05). Furthermore, denervated
CTMP knockout (
CTMP-KO) gastrocnemius weighed more than WT muscle (p < 0.05). Denervated
CTMP-KO gastrocnemius also showed higher Akt and downstream
glycogen synthase kinase 3β (GSK3β) phosphorylation compared to WT muscle (p < 0.05) as well as
ribosomal proteins S6 and 4E-BP1 phosphorylation (p < 0.001 and p < 0.05, respectively). Moreover,
CTMP-KO mice showed significantly lower levels of
E3 ubiquitin ligase MuRF-1 and
myostatin than WT muscle (p < 0.05). Our findings suggest that
CTMP is essential to
muscle atrophy after
denervation and it may act by reducing Akt signaling,
protein synthesis, and increasing myocellular catabolism.