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ANO10 在健康和疾病中的功能。

ANO10 Function in Health and Disease.

机构信息

Neurogenetics Department, The Cyprus Institute of Neurology and Genetics, Iroon Avenue 6, Agios Dometios 2371, Nicosia, Cyprus.

The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, Iroon Avenue 6, Agios Dometios 2371, Nicosia, Cyprus.

出版信息

Cerebellum. 2023 Jun;22(3):447-467. doi: 10.1007/s12311-022-01395-3. Epub 2022 Jun 1.

Abstract

Anoctamin 10 (ANO10), also known as TMEM16K, is a transmembrane protein and member of the anoctamin family characterized by functional duality. Anoctamins manifest ion channel and phospholipid scrambling activities and are involved in many physiological processes such as cell division, migration, apoptosis, cell signalling, and developmental processes. Several diseases, including neurological, muscle, blood disorders, and cancer, have been associated with the anoctamin family proteins. ANO10, which is the main focus of the present review, exhibits both scrambling and chloride channel activity; calcium availability is necessary for protein activation in either case. Additional processes implicating ANO10 include endosomal sorting, spindle assembly, and calcium signalling. Dysregulation of calcium signalling in Purkinje cells due to ANO10 defects is proposed as the main mechanism leading to spinocerebellar ataxia autosomal recessive type 10 (SCAR10), a rare, slowly progressive spinocerebellar ataxia. Regulation of the endolysosomal pathway is an additional ANO10 function linked to SCAR10 aetiology. Further functional investigation is essential to unravel the ANO10 mechanism of action and involvement in disease development.

摘要

Anoctamin 10(ANO10),也称为 TMEM16K,是一种跨膜蛋白,属于 anoctamin 家族,具有功能双重性。Anoctamins 表现出离子通道和磷脂重排活性,参与许多生理过程,如细胞分裂、迁移、凋亡、细胞信号转导和发育过程。几种疾病,包括神经、肌肉、血液疾病和癌症,与 anoctamin 家族蛋白有关。ANO10 是本综述的主要焦点,表现出重排和氯离子通道活性;在这两种情况下,钙的可用性对于蛋白质的激活都是必要的。ANO10 还涉及其他过程,包括内体分选、纺锤体组装和钙信号转导。由于 ANO10 缺陷导致 Purkinje 细胞钙信号转导失调,被认为是导致常染色体隐性遗传性 10 型脊髓小脑共济失调(SCAR10)的主要机制,这是一种罕见的、进行性缓慢的脊髓小脑共济失调。内溶酶体途径的调节是与 SCAR10 发病机制相关的 ANO10 功能的另一个附加功能。进一步的功能研究对于揭示 ANO10 的作用机制及其在疾病发展中的作用至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ed9/10126014/c1521c11a2aa/12311_2022_1395_Fig1_HTML.jpg

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