Kinetochore Proteins Have a Post-Mitotic Function in Neurodevelopment

• Published in: Developmental cell 2019-03, Vol.48 (6), p.873-882.e4
• Main Authors: Zhao, Guoli, Oztan, Asli, Ye, Yingzhi, Schwarz, Thomas L.
• Format: Article
• Language: English
• Subjects: centromere; dendrite; Drosophila; hippocampus; kinetochore; Mis12; Ndc80; neuromuscular junction; synapse
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2019.02.003

The kinetochore is a complex of proteins, broadly conserved from yeast to man, that resides at the centromere and is essential for chromosome segregation in dividing cells. There are no known functions of the core complex outside of the centromere. We now show that the proteins of the kinetochore have an essential post-mitotic function in neurodevelopment. At the embryonic neuromuscular junction of Drosophila melanogaster, mutation or knockdown of many kinetochore components cause neurites to overgrow and prevent formation of normal synaptic boutons. Kinetochore proteins were detected in synapses and axons in Drosophila. In post-mitotic cultured hippocampal neurons, knockdown of mis12 increased the filopodia-like protrusions in this region. We conclude that the proteins of the kinetochore are repurposed to sculpt developing synapses and dendrites and thereby contribute to the correct development of neuronal circuits in both invertebrates and mammals. •Kinetochore proteins act locally in development of post-mitotic Drosophila neurons•Mutations of kinetochore proteins alter synaptic morphology and neurite length•Knockdown of mis12 alters morphology of rat hippocampal dendrites The kinetochore has only been shown to function in chromosome segregation in dividing cells. Zhao et al. show that kinetochore proteins are repurposed during neuronal development and are required in the development of both fly and mammalian neurons for the correct formation of synapses and dendrites.