Bird Kalynn M, Jenkins Paul M
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, U.S.A.
Department of Psychiatry, University of Michigan Medical School, Ann Arbor, MI, U.S.A.
Biochem Soc Trans. 2025 Apr 30;53(2):497-507. doi: 10.1042/BST20253016.
Ankyrins are a family of intracellular scaffolding proteins that control the subcellular localization of a host of critically important signaling proteins within neurons, including many proteins associated with neurological disease. Ankyrin proteins are a vital component of the neuron. These scaffolding proteins must be spatially and temporally arranged to interact with their binding partners and facilitate proper neuronal signaling. Dysfunction of ankyrins is associated with neurodevelopmental disorders such as epilepsy and autism spectrum disorder. Despite the high degree of sequence similarity between ankyrin proteins, they display almost completely nonoverlapping localization and function. How ankyrins localize to the correct subcellular compartments to interact with their binding partners and complete their distinct roles remains poorly understood. Emerging evidence suggests that post-translational modifications may play a key part in this process. Some of the post-translational modifications that have been identified to regulate ankyrins are phosphorylation, ubiquitination, and palmitoylation. These modifications affect proper interactions, function, and localization of ankyrin proteins, which highlights their potential role in disease. This review will give an overview of neuronal ankyrins, and how post-translational modifications could be utilized to regulate protein localization and function in the context of neurological disease.
锚蛋白是一类细胞内支架蛋白，可控制神经元内许多至关重要的信号蛋白的亚细胞定位，其中包括许多与神经疾病相关的蛋白。锚蛋白是神经元的重要组成部分。这些支架蛋白必须在空间和时间上进行排列，以与其结合伴侣相互作用并促进正常的神经元信号传导。锚蛋白功能异常与癫痫和自闭症谱系障碍等神经发育障碍有关。尽管锚蛋白之间的序列相似性很高，但它们的定位和功能几乎完全不重叠。目前对于锚蛋白如何定位到正确的亚细胞区室以与其结合伴侣相互作用并完成其独特作用仍知之甚少。新出现的证据表明，翻译后修饰可能在这一过程中起关键作用。已确定的一些调节锚蛋白的翻译后修饰包括磷酸化、泛素化和棕榈酰化。这些修饰影响锚蛋白的正确相互作用、功能和定位，这突出了它们在疾病中的潜在作用。本综述将概述神经元锚蛋白，以及在神经疾病背景下如何利用翻译后修饰来调节蛋白质的定位和功能。
