The NDR family of kinases: essential regulators of aging

IF 3.5 3区医学 Q2 NEUROSCIENCES

Frontiers in Molecular Neuroscience Pub Date : 2024-05-13 DOI:10.3389/fnmol.2024.1371086

Kevin Jonischkies, Miguel del Angel, Yunus Emre Demiray, Allison Loaiza Zambrano, Oliver Stork

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Abstract

Aging is defined as a progressive decline of cognitive and physiological functions over lifetime. Since the definition of the nine hallmarks of aging in 2013 by López-Otin, numerous studies have attempted to identify the main regulators and contributors in the aging process. One interesting group of proteins whose participation has been implicated in several aging hallmarks are the nuclear DBF2-related (NDR) family of serine-threonine AGC kinases. They are one of the core components of the Hippo signaling pathway and include NDR1, NDR2, LATS1 and LATS2 in mammals, along with its highly conserved metazoan orthologs; Trc in Drosophila melanogaster, SAX-1 in Caenorhabditis elegans, CBK1, DBF20 in Saccharomyces cerevisiae and orb6 in Saccharomyces pombe. These kinases have been independently linked to the regulation of widely diverse cellular processes disrupted during aging such as the cell cycle progression, transcription, intercellular communication, nutrient homeostasis, autophagy, apoptosis, and stem cell differentiation. However, a comprehensive overview of the state-of-the-art knowledge regarding the post-translational modifications of and by NDR kinases in aging has not been conducted. In this review, we summarize the current understanding of the NDR family of kinases, focusing on their relevance to various aging hallmarks, and emphasize the growing body of evidence that suggests NDR kinases are essential regulators of aging across species.

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NDR 激酶家族：衰老的重要调节因子

衰老被定义为一生中认知和生理功能的逐渐衰退。自2013年洛佩斯-奥廷（López-Otin）定义了九大衰老标志以来，许多研究都试图找出衰老过程中的主要调控因子和促成因素。其中一组有趣的蛋白质是丝氨酸-苏氨酸AGC激酶的核DBF2相关（NDR）家族，它们参与了多个衰老标志。它们是 Hippo 信号通路的核心成分之一，包括哺乳动物中的 NDR1、NDR2、LATS1 和 LATS2，以及高度保守的后生动物同源物：黑腹果蝇中的 Trc、秀丽隐杆线虫中的 SAX-1、CBK1、酿酒酵母中的 DBF20 和酿酒酵母中的 orb6。这些激酶与衰老过程中被破坏的多种细胞过程（如细胞周期进展、转录、细胞间通讯、营养平衡、自噬、细胞凋亡和干细胞分化）的调控有着独立的联系。然而，有关衰老过程中 NDR 激酶的翻译后修饰以及 NDR 激酶的翻译后修饰的最新知识还没有进行过全面的综述。在这篇综述中，我们总结了目前对 NDR 激酶家族的了解，重点关注它们与各种衰老特征的相关性，并强调越来越多的证据表明 NDR 激酶是跨物种衰老的重要调节因子。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Molecular Neuroscience NEUROSCIENCES-

CiteScore

5.70

自引率

2.10%

发文量

669

审稿时长

14 weeks

期刊介绍： Frontiers in Molecular Neuroscience is a first-tier electronic journal devoted to identifying key molecules, as well as their functions and interactions, that underlie the structure, design and function of the brain across all levels. The scope of our journal encompasses synaptic and cellular proteins, coding and non-coding RNA, and molecular mechanisms regulating cellular and dendritic RNA translation. In recent years, a plethora of new cellular and synaptic players have been identified from reduced systems, such as neuronal cultures, but the relevance of these molecules in terms of cellular and synaptic function and plasticity in the living brain and its circuits has not been validated. The effects of spine growth and density observed using gene products identified from in vitro work are frequently not reproduced in vivo. Our journal is particularly interested in studies on genetically engineered model organisms (C. elegans, Drosophila, mouse), in which alterations in key molecules underlying cellular and synaptic function and plasticity produce defined anatomical, physiological and behavioral changes. In the mouse, genetic alterations limited to particular neural circuits (olfactory bulb, motor cortex, cortical layers, hippocampal subfields, cerebellum), preferably regulated in time and on demand, are of special interest, as they sidestep potential compensatory developmental effects.