Graded Control of Microtubule Severing by Tubulin Glutamylation.
Graded Control of Microtubule Severing by Tubulin Glutamylation.
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DOI：
10.1016/j.cell.2016.01.019
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发表时间：
2016-02-25
期刊：
影响因子：
64.5
通讯作者：
Roll-Mecak A
中科院分区：
文献类型：
--
作者：
Valenstein ML;Roll-Mecak A
Microtubule-severing enzymes are critical for the biogenesis and maintenance of complex microtubule arrays in axons, spindles and cilia where tubulin detyrosination, acetylation and glutamylation are abundant. These modifications exhibit stereotyped patterns suggesting spatial and temporal control of microtubule functions. Using human engineered and differentially modified microtubules we find that glutamylation is the main regulator of the hereditary spastic paraplegia microtubule severing enzyme spastin. Glutamylation acts as a rheostat and tunes microtubule severing as a function of glutamate number added per tubulin. Unexpectedly, glutamylation is a nonlinear biphasic tuner and becomes inhibitory beyond a threshold. Furthermore, the inhibitory effect of localized glutamylation propagates across neighboring microtubules, modulating severing in trans. Our work provides the first quantitative evidence for a graded response to a tubulin posttranslational modification and a biochemical link between tubulin glutamylation and complex architectures of microtubule arrays such as those in neurons where spastin deficiency causes disease. Glutamylation acts as a rheostat that tunes microtubule severing as a function of the number of glutamate molecules added per tubulin to maintain the complex architectures of microtubule arrays.
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影响因子：
30.8
作者：
Lee, Ji Eun;Silhavy, Jennifer L.;Zaki, Maha S.;Schroth, Jana;Bielas, Stephanie L.;Marsh, Sarah E.;Olvera, Jesus;Brancati, Francesco;Iannicelli, Miriam;Ikegami, Koji;Schlossman, Andrew M.;Merriman, Barry;Attie-Bitach, Tania;Logan, Clare V.;Glass, Ian A.;Cluckey, Andrew;Louie, Carrie M.;Lee, Jeong Ho;Raynes, Hilary R.;Rapin, Isabelle;Castroviejo, Ignacio P.;Setou, Mitsutoshi;Barbot, Clara;Boltshauser, Eugen;Nelson, Stanley F.;Hildebrandt, Friedhelm;Johnson, Colin A.;Doherty, Daniel A.;Valente, Enza Maria;Gleeson, Joseph G.
通讯作者：
Gleeson, Joseph G.
影响因子：
3.7
作者：
Eckert T;Le DT;Link S;Friedmann L;Woehlke G
通讯作者：
Woehlke G
影响因子：
64.5
作者：
Garnham CP;Vemu A;Wilson-Kubalek EM;Yu I;Szyk A;Lander GC;Milligan RA;Roll-Mecak A
通讯作者：
Roll-Mecak A
影响因子：
56.9
作者：
Guizetti, Julien;Schermelleh, Lothar;Gerlich, Daniel W.
通讯作者：
Gerlich, Daniel W.
影响因子：
56.9
作者：
Hartman, JJ;Vale, RD
通讯作者：
Vale, RD