Heterodimeric capping protein is required for stereocilia length and width regulation.
Heterodimeric capping protein is required for stereocilia length and width regulation.
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DOI：
10.1083/jcb.201704171
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发表时间：
2017-11-06
期刊：
影响因子：
--
通讯作者：
Barr-Gillespie PG
中科院分区：
文献类型：
--
作者：
Avenarius MR;Krey JF;Dumont RA;Morgan CP;Benson CB;Vijayakumar S;Cunningham CL;Scheffer DI;Corey DP;Müller U;Jones SM;Barr-Gillespie PG
作者表明，异二聚体加帽蛋白亚基CAPZB在内耳的静纤毛、肌动蛋白填充过程的发育过程中是必需的。他们发现CAPZB在静纤毛变宽的发育阶段阻止了新形成的肌动蛋白丝的解聚。肌动蛋白丰富的过程，如丝状伪足，片状伪足，微绒毛，静纤毛的尺寸控制需要许多蛋白质的协调活动。这些肌动蛋白结构中的每一个都依赖于异二聚体加帽蛋白（CAPZ），其在倒刺末端阻断肌动蛋白聚合。由于内耳静纤毛的尺寸控制特别精确，我们研究了毛细胞中的CAPZB亚基。CAPZB以每静纤毛约100个拷贝的量存在，随着毛细胞发育的进展，CAPZB集中在静纤毛尖端，类似于CAPZB相互作用蛋白TWF 2。我们使用Atoh 1-Cre删除了毛细胞中的Capzb，消除了听觉和前庭功能。CAPZB无效静纤毛最初正常发展，但后来缩短和消失，令人惊讶的是，静纤毛宽度减少伴随着长度。子宫内电穿孔表达CAPZB 2阻止前庭静纤毛的正常伸长，并使其不规则地变宽。总之，这些结果表明，加帽蛋白参与静纤毛扩大，防止新伸长的肌动蛋白丝解聚。
The authors show that the heterodimeric capping protein subunit CAPZB is required during development of stereocilia, actin-filled processes of the inner ear. They find that CAPZB prevents depolymerization of newly formed actin filaments during the developmental stage when stereocilia widen. Control of the dimensions of actin-rich processes like filopodia, lamellipodia, microvilli, and stereocilia requires the coordinated activity of many proteins. Each of these actin structures relies on heterodimeric capping protein (CAPZ), which blocks actin polymerization at barbed ends. Because dimension control of the inner ear’s stereocilia is particularly precise, we studied the CAPZB subunit in hair cells. CAPZB, present at ∼100 copies per stereocilium, concentrated at stereocilia tips as hair cell development progressed, similar to the CAPZB-interacting protein TWF2. We deleted Capzb specifically in hair cells using Atoh1-Cre, which eliminated auditory and vestibular function. Capzb-null stereocilia initially developed normally but later shortened and disappeared; surprisingly, stereocilia width decreased concomitantly with length. CAPZB2 expressed by in utero electroporation prevented normal elongation of vestibular stereocilia and irregularly widened them. Together, these results suggest that capping protein participates in stereocilia widening by preventing newly elongating actin filaments from depolymerizing.
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影响因子：
9.8
作者：
Hertzog M;Milanesi F;Hazelwood L;Disanza A;Liu H;Perlade E;Malabarba MG;Pasqualato S;Maiolica A;Confalonieri S;Le Clainche C;Offenhauser N;Block J;Rottner K;Di Fiore PP;Carlier MF;Volkmann N;Hanein D;Scita G
通讯作者：
Scita G
影响因子：
4.4
作者：
Erde, Jonathan;Loo, Rachel R. Ogorzalek;Loo, Joseph A.
通讯作者：
Loo, Joseph A.
影响因子：
5.3
作者：
Canton, DA;Olsten, MEK;Litchfield, DW
通讯作者：
Litchfield, DW
影响因子：
4.4
作者：
Cox, Juergen;Neuhauser, Nadin;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
1.6
作者：
Kanzaki, S;Beyer, LA;Raphael, Y
通讯作者：
Raphael, Y