The Kinesin KIF21B Regulates Microtubule Dynamics and Is Essential for Neuronal Morphology, Synapse Function, and Learning and Memory.
The Kinesin KIF21B Regulates Microtubule Dynamics and Is Essential for Neuronal Morphology, Synapse Function, and Learning and Memory.
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DOI：
10.1016/j.celrep.2016.03.086
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发表时间：
2016-05-03
期刊：
影响因子：
8.8
通讯作者：
Kneussel M
中科院分区：
文献类型：
--
作者：
Muhia M;Thies E;Labonté D;Ghiretti AE;Gromova KV;Xompero F;Lappe-Siefke C;Hermans-Borgmeyer I;Kuhl D;Schweizer M;Ohana O;Schwarz JR;Holzbaur ELF;Kneussel M
驱动蛋白KIF21B与几种人类神经系统疾病有关，包括认知发育延迟，但目前尚不清楚KIF21B功能障碍如何导致病理学。一个局限性是对KIF21B介导的生理机制知之甚少。在这里，我们产生了Kif21b基因敲除小鼠，并使用细胞测定来研究KIF21B在神经元和体内功能中的相关性。我们表明，KIF21 B是一个进行性电机，并确定一个额外的作用KIF21 B在调节微管动力学。在缺乏KIF21B的神经元中，微管生长得更慢，更持久，导致树突中的包装更紧密。KIF21B缺陷神经元表现出树突乔木复杂性降低和棘密度降低，这与突触传递缺陷相关。与这些观察结果一致，KIF21B基因敲除小鼠表现出涉及学习和记忆缺陷的行为变化。总的来说，我们的研究提供了对KIF21B细胞功能的深入了解，以及KIF21B失调导致认知功能下降的基础。
The kinesin KIF21B is implicated in several human neurological disorders including delayed cognitive development, yet it remains unclear how KIF21B dysfunction may contribute to pathology. One limitation is that relatively little is known about KIF21B-mediated physiological mechanisms. Here, we generated Kif21b knockout mice and used cellular assays to investigate the relevance of KIF21B in neuronal and in vivo function. We show that KIF21B is a processive motor, and identify an additional role for KIF21B in regulating microtubule dynamics. In neurons lacking KIF21B, microtubules grow more slowly and persistently, leading to tighter packing in dendrites. KIF21B-deficient neurons exhibit decreased dendritic arbor complexity and reduced spine density, which correlate with deficits in synaptic transmission. Consistent with these observations, KIF21B-null mice exhibit behavioral changes involving learning and memory deficits. Collectively, our study provides insight into the cellular function of KIF21B and the basis for cognitive decline resulting from KIF21B dysregulation.