Key result
The KY protein interacts with and degrades filamin C, and KY deficiency in mice leads to irregular subcellular localization of filamin C in muscle fibres.
KY-filamin C interaction merits human myopathy studies; leaves open its role in muscle disease pathogenesis.
The KY protein has been implicated in a neuromuscular dystrophy in the mouse, but its role in muscle function remains unclear. Here, we show that KY interacts with several sarcomeric cytoskeletal proteins including, amongst others, filamin C and the slow isoform of the myosin-binding protein C. These interactions were confirmed in vitro and because of its central role in skeletal muscle disease, characterized in more detail for filamin C. A role for KY in regulating filamin C function in vivo is supported by the expression analysis of filamin C in the null ky mouse mutant, where distinct irregular subcellular localization of filamin C was found in subsets of muscle fibres, which appears to be a specific outcome of KY deficiency. Furthermore, KY shows protease activity in in vitro assays, and specific degradation of filamin C by KY is shown in transfected cells. Given the enzymatic nature of the KY protein, it is likely that some of the identified partners are catalytic substrates. These results suggest that KY is an intrinsic part of the protein networks underlying the molecular mechanism of several limb-girdle muscular dystrophies, particularly those where interactions between filamin C and disease causing proteins have been shown.
No takes yet. Share an insight, caveat, or question.
Beatham et al. (2004) studied Neuromuscular dystrophy. KY protein deficiency was evaluated on Protein interactions and subcellular localization of filamin C. The KY protein interacts with and degrades filamin C, and KY deficiency in mice leads to irregular subcellular localization of filamin C in muscle fibres.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: