The non-catalytic domains of Drosophila katanin regulate its abundance and microtubule-disassembly activity.
The non-catalytic domains of Drosophila katanin regulate its abundance and microtubule-disassembly activity.
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DOI：
10.1371/journal.pone.0123912
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Rogers SL
中科院分区：
文献类型：
--
作者：
Grode KD;Rogers SL
微管切断是一种在微管中产生内部断裂的生物化学反应，并且微管切断的调节对于细胞过程如纤毛发生、形态发生以及减数分裂和有丝分裂至关重要。Katanin是一种保守的异源二聚体ATP酶，它能切断和分解微管，但其调控微管切断的分子决定因素仍不清楚。在这里，我们表明，果蝇katanin的非催化结构域调节其在活细胞中的丰度和活性。我们的数据表明，微管相互作用和贩运（MIT）域和相邻的连接区的果蝇katanin催化亚基Kat60合作，以两种不同的方式调节微管切断。首先，Kat60的MIT结构域和接头区通过增强其蛋白酶体依赖性降解而降低其丰度。果蝇katanin调节亚基Kat80，这是需要在细胞中稳定Kat60，反过来减少蛋白酶体依赖性降解Kat60。其次，MIT结构域和连接区的Kat60增加其微管拆卸活动，通过增强其与微管。在我们的数据的基础上，我们提出，果蝇katanin的非催化结构域作为整合的监管输入的主要网站，从而控制其切断和拆卸微管的能力。
Microtubule severing is a biochemical reaction that generates an internal break in a microtubule and regulation of microtubule severing is critical for cellular processes such as ciliogenesis, morphogenesis, and meiosis and mitosis. Katanin is a conserved heterodimeric ATPase that severs and disassembles microtubules, but the molecular determinants for regulation of microtubule severing by katanin remain poorly defined. Here we show that the non-catalytic domains of Drosophila katanin regulate its abundance and activity in living cells. Our data indicate that the microtubule-interacting and trafficking (MIT) domain and adjacent linker region of the Drosophila katanin catalytic subunit Kat60 cooperate to regulate microtubule severing in two distinct ways. First, the MIT domain and linker region of Kat60 decrease its abundance by enhancing its proteasome-dependent degradation. The Drosophila katanin regulatory subunit Kat80, which is required to stabilize Kat60 in cells, conversely reduces the proteasome-dependent degradation of Kat60. Second, the MIT domain and linker region of Kat60 augment its microtubule-disassembly activity by enhancing its association with microtubules. On the basis of our data, we propose that the non-catalytic domains of Drosophila katanin serve as the principal sites of integration of regulatory inputs, thereby controlling its ability to sever and disassemble microtubules.
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