Expression of Ankrd2 in fast and slow muscles and its response to stretch are consistent with a role in slow muscle...

In striated muscle, the structural genes associated with muscle fiber phenotype determination as well as muscle mass accretion are regulated largely by mechanical stimuli. Passive stretch of skeletal muscle stimulates muscle growth/hypertrophy and an increased expression of slow muscle genes. We previously identified Ankyrin repeat-domain protein (Ankrd2) as a novel transcript expressed in fast tibialis anterior muscles after 7 days of passive stretch immobilization in vivo. Here, we test the hypothesis that the expression of Ankrd2 in stretched fast muscle is associated with the stretch-induced expression of slow muscle phenotype rather than the hypertrophic response. Our results show that, in 4- and 7-day stretched tibialis anterior muscle, the expression of Ankrd2 mRNA and protein was significantly upregulated (P > 0.001). However, in fast muscles of kyphoscoliotic mutant mice, which lack the hypertrophic response to overload but have a slower muscle phenotype than wild-type, Ankrd2 expression was significantly upregulated. The distribution pattern of Ankrd2 in fast and slow muscle is also in accord with their slow fiber composition. Furthermore, it was markedly downregulated in denervated rat soleus muscle, which produces a pronounced shift toward the fast muscle phenotype. Using a sensitive proteomics approach (Ciphergen Technology), we observed that Ankrd2 protein was undetectable in soleus after 4 wk of denervation. We suggest that Ankrd2, which is also a titin binding protein, is a stretch-response gene associated with slow muscle function and that it is part of a separate mechanotransduction system to the one that regulates muscle mass.