A troponin switch that regulates muscle contraction by stretch instead of calcium

A troponin switch that regulates muscle contraction by stretch instead of calcium
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DOI:
10.1038/sj.emboj.7600097
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发表时间:
2004-02-25
期刊:
影响因子:
11.4
通讯作者:
Bullard, B
Bullard, B
中科院分区:
生物学1区
文献类型:
--
作者:
Agianian, B;Krzic, U;Bullard, B

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许多昆虫的飞行肌肉都有一种调节形式,使它们能够高频收缩。低 Ca2+ 水平下的周期性伸展可以激活肌肉。相同的肌肉也会响应较高的 Ca2+ 而产生等长收缩。我们证明这两种活性是由单个肌原纤维内不同的 TnC 同工型(F1 和 F2)控制的。 F1 在 C 端结构域中以高亲和力结合一种 Ca2+,F2 在 C 端结构域中结合一种 Ca2+,在 N 端结构域中结合一种可交换的 Ca2+。我们通过用重组异构体取代 Lethocerus 飞行肌纤维中的内源性 TnC,对异构体进行了表征,并确定了它们对拉伸激活和 Ca2+ 激活张力的发展的影响。具有 F1 的纤维具有拉伸激活张力和最小等长张力; F2 组给予 Ca2+ 依赖的等长张力和最小的拉伸激活张力。 TnC 响应拉伸而不是 Ca2+ 的调节是前所未有的,并且导致昆虫飞行肌肉在低 Ca2+ 浓度下执行振荡工作的能力,大量飞行昆虫的进化成功归功于这一特性。
The flight muscles of many insects have a form of regulation enabling them to contract at high frequencies. The muscles are activated by periodic stretches at low Ca2+ levels. The same muscles also give isometric contractions in response to higher Ca2+. We show that the two activities are controlled by different isoforms of TnC (F1 and F2) within single myofibrils. F1 binds one Ca2+ with high affinity in the C-terminal domain and F2 binds one Ca2+ in the C-terminal domain and one exchangeable Ca2+ in the N-terminal domain. We have characterised the isoforms and determined their effect on the development of stretch-activated and Ca2+-activated tension by replacing endogenous TnC in Lethocerus flight muscle fibres with recombinant isoforms. Fibres with F1 gave stretch-activated tension and minimal isometric tension; those with F2 gave Ca2+-dependent isometric tension and minimal stretch-activated tension. Regulation by a TnC responding to stretch rather than Ca2+ is unprecedented and has resulted in the ability of insect flight muscle to perform oscillatory work at low Ca2+ concentrations, a property to which a large number of flying insects owe their evolutionary success.