title: Axonal pruning is actively regulated by the microtubule-destabilizing protein kinesin superfamily protein 2A.
abstract: Extensive axonal pruning and neuronal cell death are critical events for the development of the nervous system. Like neuronal cell death, axonal elimination occurs in discrete steps; however, the regulators of these processes remain mostly elusive. Here, we identify the kinesin superfamily protein 2A (KIF2A) as a key executor of microtubule disassembly and axonal breakdown during axonal pruning. Knockdown of Kif2a, but not other microtubule depolymerization or severing proteins, protects axonal microtubules from disassembly upon trophic deprivation. We further confirmed and extended this result to demonstrate that the entire degeneration process is delayed in neurons from the Kif2a knockout mice. Finally, we show that the Kif2a-null mice exhibit normal sensory axon patterning early during development, but abnormal target hyperinnervation later on, as they compete for limited skin-derived trophic support. Overall, these findings reveal a central regulatory mechanism of axonal pruning during development.
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Maor-Nof
authors.forename: Noriko
authors.initials: N
authors.lastname: Homma
authors.forename: Calanit
authors.initials: C
authors.lastname: Raanan
authors.forename: Aviv
authors.initials: A
authors.lastname: Nof
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hirokawa
authors.forename: Avraham
authors.initials: A
authors.lastname: Yaron
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000166:cytology; D016547:Kinesins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D058105:Polymerization / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D012097:Repressor Proteins; D016875:tau Proteins; C477238:KIF2A protein, mouse; D016547:Kinesins; D017239:Paclitaxel