1. KIF2A deficiency causes early-onset neurodegeneration
- Author
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Nuria Ruiz-Reig, Georges Chehade, Janne Hakanen, Mohamed Aittaleb, Keimpe Wierda, Joris De Wit, Laurent Nguyen, Philippe Gailly, Fadel Tissir, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire
- Subjects
neuronal polarity ,PROVIDES ,Neurons ,Brain Diseases ,Science & Technology ,Multidisciplinary ,neurodevelopment ,ELONGATION ,PROTEINS ,neurodegeneration ,Kinesins ,Microtubules ,Multidisciplinary Sciences ,REGULATES MICROTUBULE DYNAMICS ,Repressor Proteins ,Mice ,brain wiring ,Science & Technology - Other Topics ,Animals ,KINESIN ,MALFORMATIONS ,PURKINJE-CELL DEGENERATION ,MUTATION ,IN-VIVO ,SUPPRESSION - Abstract
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. ispartof: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA vol:119 issue:46 ispartof: location:United States status: published
- Published
- 2023