微管蛋白是微管的高度保守的亚基,涉及各种基本功能,包括大脑发育。微管有助于神经元增殖,迁移,分化,沿着轴突的货物运输,突触形成,还有更多。由多个同种型组成的微管蛋白基因家族,它们的差异表达和不同的翻译后修饰在完成多种神经元功能方面创造了一个全新的复杂性和多样性水平。对微管蛋白基因与大脑发育关系的研究为了解每种微管蛋白同种型在神经发育中的作用开辟了新的途径。据报道,微管蛋白基因突变会导致大脑发育缺陷,尤其是皮质畸形,称为微管病。越来越需要了解各种微管蛋白突变与相关脑病理学之间的分子相关性。最近,微管蛋白同种型突变(TUBA1A,TUBB,TUBB1,TUBB2A,TUBB2B,TUBB3和TUBG1)已与引起各种神经发育缺陷有关,例如小脑,小头畸形,皮质发育不良,polymicrogyria,脑裂,皮质下频带异托邦,脑室周围异位症,call体发育不全,和小脑发育不全.这篇综述总结了微管动力学,它们在神经发育中的作用,微管蛋白同种型,翻译后修饰,以及微管蛋白突变在引起特定神经发育缺陷中的作用。已经准备了一份包含所有报道的与脑发育缺陷相关的微管蛋白致病变异的综合清单,以给出广泛的微管蛋白功能的鸟瞰。
Tubulins are the highly conserved subunit of microtubules which involve in various fundamental functions including brain development. Microtubules help in neuronal proliferation, migration, differentiation, cargo transport along the axons, synapse formation, and many more. Tubulin gene family consisting of multiple isotypes, their differential expression and varied post translational modifications create a whole new level of complexity and diversity in accomplishing manifold neuronal functions. The studies on the relation between tubulin genes and brain development opened a new avenue to understand the role of each tubulin isotype in neurodevelopment. Mutations in tubulin genes are reported to cause brain development defects especially cortical malformations, referred as tubulinopathies. There is an increased need to understand the molecular correlation between various tubulin mutations and the associated brain pathology. Recently, mutations in tubulin isotypes (TUBA1A, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB3, and TUBG1) have been linked to cause various neurodevelopmental defects like lissencephaly, microcephaly, cortical dysplasia, polymicrogyria, schizencephaly, subcortical band heterotopia, periventricular heterotopia, corpus callosum agenesis, and cerebellar hypoplasia. This review summarizes on the microtubule dynamics, their role in neurodevelopment, tubulin isotypes, post translational modifications, and the role of tubulin mutations in causing specific neurodevelopmental defects. A comprehensive list containing all the reported tubulin pathogenic variants associated with brain developmental defects has been prepared to give a bird\'s eye view on the broad range of tubulin functions.