CLASP promotes microtubule rescue by recruiting tubulin dimers to the microtubule.

CLASP promotes microtubule rescue by recruiting tubulin dimers to the microtubule.
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DOI:
10.1016/j.devcel.2010.07.016
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发表时间:
2010-08-17
期刊:
影响因子:
11.8
通讯作者:
Chang, Fred
Chang, Fred
中科院分区:
生物学1区
文献类型:
--
作者:
Al-Bassam, Jawdat;Kim, Hwajin;Brouhard, Gary;van Oijen, Antoine;Harrison, Stephen C.;Chang, Fred

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微管(MT)动力学的空间调节有助于细胞的极性和细胞分裂。MT救援,即MT停止收缩并重新启动增长,是MT动态中最不为人所知的方面。细胞质连接物相关蛋白(CLAPS)是一类保守的MT相关蛋白,在体内有助于MT的稳定和拯救。我们在这里证明了裂殖酵母CLS1P是一种同源二聚体,它通过保守的TOG样结构域与αβ微管蛋白异源二聚体结合。在体外,CLAP可增加MT救援频率,减少MT突变频率,并适度降低MT解离率。卡环稳定地结合在MT晶格上,招募微管蛋白,并在局部促进救援。CLAP TOG结构域的突变表明,微管蛋白结合对其救援活性至关重要。我们提出了一种拯救机制,即扣-微管蛋白二聚体复合体沿着MT晶格结合,并与其结合的微管蛋白二聚体反向解聚MT。
Spatial regulation of microtubule (MT) dynamics contributes to cell polarity and cell division. MT rescue, in which a MT stops shrinking and reinitiates growth, is the least understood aspect of MT dynamics. Cytoplasmic Linker Associated Proteins (CLASPs) are a conserved class of MT-associated proteins that contribute to MT stabilization and rescue in vivo. We show here that the Schizosaccharomyces pombe CLASP, Cls1p, is a homodimer that binds an αβ tubulin heterodimer through conserved TOG-like domains. In vitro, CLASP increases MT rescue frequency, decreases MT catastrophe frequency and moderately decreases MT disassembly rate. CLASP binds stably to the MT lattice, recruits tubulin and locally promotes rescues. Mutations in the CLASP TOG domains demonstrate that tubulin binding is critical for its rescue activity. We propose a mechanism for rescue in which CLASP-tubulin dimer complexes bind along the MT lattice and reverse MT depolymerization with their bound tubulin dimer.
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