Stathmin family protein SCG10 differentially regulates the plus and minus end dynamics of microtubules at steady state in vitro:: Implications for its role in neurite outgrowth
Stathmin family protein SCG10 differentially regulates the plus and minus end dynamics of microtubules at steady state in vitro:: Implications for its role in neurite outgrowth
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DOI：
10.1021/bi061819d
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发表时间：
2007-03-20
期刊：
影响因子：
2.9
通讯作者：
Wilson, Leslie
中科院分区：
文献类型：
--
作者：
Manna, Tapas;Grenningloh, Gabriele;Wilson, Leslie
SCG 10（上级颈神经节神经特异性10蛋白）是微管调节蛋白的stathmin家族的神经元特异性成员，其像stathmin一样可以结合可溶性微管蛋白和去微管蛋白。SCG10对微管本身及其动力学的直接作用以前没有研究过。在这里，我们分析了SCG10对微管在体外的动态不稳定行为的影响，无论是在稳态和早期微管聚合。与Stathmin相反，Stathmin对动力学的主要作用是通过增加微管末端从生长到缩短的切换频率（突变频率）来破坏微管的稳定，SCG10通过增加生长的速率和程度在稳定状态和聚合过程中的早期稳定了正末端。例如，在高初始微管蛋白浓度（20 μ M）的聚合早期，SCG 10与微管蛋白的1：30的低摩尔比使生长速率增加了约50%。与其对正末端的影响相反，SCG 10通过增加缩短速率、缩短事件期间缩短的长度和突变频率来使负末端不稳定。与其在稳态下调节微管动力学的能力一致，SCG 10沿其长度沿着与纯化的微管结合。SCG10在相对微管末端的双重活性对于其调节生长锥微管动力学的作用可能是重要的。SCG10促进正末端生长的能力可能有助于微管延伸到丝状伪足中，并且其使负末端不稳定的能力可能为净正末端延伸提供可溶性微管蛋白。
SCG10 (superior cervical ganglia neural-specific 10 protein) is a neuron specific member of the stathmin family of microtubule regulatory proteins that like stathmin can bind to soluble tubulin and depolymerize microtubules. The direct actions of SCG10 on microtubules themselves and on their dynamics have not been investigated previously. Here, we analyzed the effects of SCG10 on the dynamic instability behavior of microtubules in vitro, both at steady state and early during microtubule polymerization. In contrast to stathmin, whose major action on dynamics is to destabilize microtubules by increasing the switching frequency from growth to shortening (the catastrophe frequency) at microtubule ends, SCG10 stabilized the plus ends both at steady state and early during polymerization by increasing the rate and extent of growth. For example, early during polymerization at high initial tubulin concentrations (20 mu M), a low molar ratio of SCG10 to tubulin of 1:30 increased the growth rate by similar to 50%. In contrast to its effects at plus ends, SCG10 destabilized minus ends by increasing the shortening rate, the length shortened during shortening events, and the catastrophe frequency. Consistent with its ability to modulate microtubule dynamics at steady state, SCG10 bound to purified microtubules along their lengths. The dual activity of SCG10 at opposite microtubule ends may be important for its role in regulating growth cone microtubule dynamics. SCG10's ability to promote plus end growth may facilitate microtubule extension into filopodia, and its ability to destabilize minus ends could provide soluble tubulin for net plus end elongation.