Mechanism of Catch Force: Tethering of Thick andThin Filaments by Twitchin

[摘要] Catch is a mechanical state occurring in some invertebrate smooth muscles characterizedby high force maintenance and resistance to stretch during extremely slow relaxation. During catch, intracellular calcium is near basal concentration and myosin crossbridgecyctng rate is extremely slow. Catch force is relaxed by a protein kinase A-mediatedphosphorylation of sites near the N- and C- temini of the minititin twitchin (~526 kDa). Some catch force maintenance car also occur together with cycling myosin crossbridgesat submaximal calcium concentrations, but not when the muscle is maximally activated. Additionally, the link responsible for catch can adjust during shortening of submaximallyactivated muscles and maintain catch force at the new shorter length. Twitchin binds toboth thick and thin filaments, and the thin filament binding shown by both the N- and Cterminalportions of twitchin is decreased by phosphorylation of the sites that regulatecatch. The data suggest that the twitchin molecule itself is the catch force beanng tetherbetween thick and thin filaments. We present a model for the regulation of catch inwhich the twitchin tether can be displaced from thin filaments by both (a) thephosphorylation of twitchin and (b) the attachment of high force myosin crossbridges.

[学科分类] 基础医学