突触发生
神经退行性变
神经发生
神经科学
生物
轴浆运输
微管
皮质神经元
驱动蛋白
细胞生物学
医学
内科学
疾病
作者
Nuria Ruiz-Reig,Georges Chehade,Janne Hakanen,Mohamed Aittaleb,Keimpe D. Wierda,Joris de Wit,Laurent Nguyen,Philippe Gailly,Fadel Tissir
标识
DOI:10.1073/pnas.2209714119
摘要
KIF2A is an atypical kinesin that has the capacity to depolymerize microtubules. Patients carrying mutations in KIF2A suffer from progressive microcephaly and mental disabilities. While the role of this protein is well documented in neuronal migration, the relationship between its dysfunction and the pathobiology of brain disorders is unclear. Here, we report that KIF2A is dispensable for embryogenic neurogenesis but critical in postnatal stages for maturation, connectivity, and maintenance of neurons. We used a conditional approach to inactivate KIF2A in cortical progenitors, nascent postmitotic neurons, and mature neurons in mice. We show that the lack of KIF2A alters microtubule dynamics and disrupts several microtubule-dependent processes, including neuronal polarity, neuritogenesis, synaptogenesis, and axonal transport. KIF2A-deficient neurons exhibit aberrant electrophysiological characteristics, neuronal connectivity, and function, leading to their loss. The role of KIF2A is not limited to development, as fully mature neurons require KIF2A for survival. Our results emphasize an additional function of KIF2A and help explain how its mutations lead to brain disorders.
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