KIF2A deficiency causes early-onset neurodegeneration
(2022) Proceedings of the National academy of sciences of the United States of America — Vol. 119, n° 46, p. e2209714119 [1-11] (2022)
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- Authors
Ruiz Reig, Nuria 
Aittaleb, Mohamed Tissir, Fadel
- Abstract
- KIF2A is an atypical kinesin that has the capacity to depolymerize microtubules. Patients carrying mutations in KIF2A suffer from progressive microcephaly and mental disabil- ities. While the role of this protein is well documented in neuronal migration, the rela- tionship 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 microtu- bule 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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Citations
Ruiz Reig, N., Chehade, G., Hakanen, J. T., Aittaleb, M., Wierda, K., De Wit, J., Nguyen, L., Gailly, P., & Tissir, F. (2022). KIF2A deficiency causes early-onset neurodegeneration. Proceedings of the National academy of sciences of the United States of America, 119(46), e2209714119 [1-11]. https://doi.org/10.1073/pnas.2209714119 (Original work published 2022)