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激酶依赖性纤毛蛋白转运调控及其治疗意义。

Kinase-dependent regulation of ciliary protein transport and its implications for therapy.

作者信息

Chaya Taro, Ayano Yuri, Furukawa Takahisa

机构信息

Laboratory for Molecular and Developmental Biology, Institute for Protein Research, The University of Osaka, Osaka, Japan.

出版信息

Front Mol Biosci. 2025 Jun 25;12:1638737. doi: 10.3389/fmolb.2025.1638737. eCollection 2025.

Abstract

Primary cilia are evolutionarily conserved microtubule-based structures that extend from the surfaces of many different cell types and decode a wide range of extracellular chemical and physical stimuli. Ciliary defects cause human diseases, termed ciliopathies, which are characterized by a variety of symptoms, such as developmental and sensory abnormalities. The formation and function of primary cilia depend on intraflagellar transport (IFT), which is a bidirectional protein transport system coordinated by three multi-subunit protein complexes with kinesin and dynein motors along the ciliary axoneme. Accumulating evidence has demonstrated that several serine-threonine kinases play key roles in the regulation of IFT. Here, we review the current understanding of the roles of these kinases during the IFT process, as well as their regulatory mechanisms, physiological and pathophysiological significance, and potential to treat ciliopathies and age-related obesity.

摘要

初级纤毛是基于微管的结构,在进化上高度保守,从许多不同类型细胞的表面伸出,可解码多种细胞外化学和物理刺激。纤毛缺陷会导致人类疾病,即纤毛病,其特征是出现各种症状,如发育和感觉异常。初级纤毛的形成和功能依赖于鞭毛内运输(IFT),这是一种双向蛋白质运输系统,由三种多亚基蛋白质复合物与驱动蛋白和动力蛋白沿着纤毛轴丝协调运作。越来越多的证据表明,几种丝氨酸 - 苏氨酸激酶在IFT的调节中起关键作用。在这里,我们综述了目前对这些激酶在IFT过程中的作用、它们的调节机制、生理和病理生理意义以及治疗纤毛病和与年龄相关的肥胖症的潜力的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a868/12237634/8fed3fa9863d/fmolb-12-1638737-g001.jpg

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