Molecular Motor KIF5A Is Essential for GABAA Receptor Transport, and KIF5A Deletion Causes Epilepsy

Kazuo Nakajima, Xiling Yin, Yosuke Takei, Dae Hyun Seog, Noriko Homma, Nobutaka Hirokawa

Research output: Contribution to journalArticle

Abstract

KIF5 (also known as kinesin-1) family members, consisting of KIF5A, KIF5B, and KIF5C, are microtubule-dependent molecular motors that are important for neuronal function. Among the KIF5s, KIF5A is neuron specific and highly expressed in the central nervous system. However, the specific roles of KIF5A remain unknown. Here, we established conditional Kif5a-knockout mice in which KIF5A protein expression was postnatally suppressed in neurons. Epileptic phenotypes were observed by electroencephalogram abnormalities in knockout mice because of impaired GABAA receptor (GABAAR)-mediated synaptic transmission. We also identified reduced cell surface expression of GABAAR in knockout neurons. Importantly, we identified that KIF5A specifically interacted with GABAAR-associated protein (GABARAP) that is known to be involved in GABAAR trafficking. KIF5A regulated neuronal surface expression of GABAARs via an interaction with GABARAP. These results provide an insight into the molecular mechanisms of KIF5A, which regulate inhibitory neural transmission.

Original languageEnglish (US)
Pages (from-to)945-961
Number of pages17
JournalNeuron
Volume76
Issue number5
DOIs
StatePublished - Dec 6 2012

ASJC Scopus subject areas

  • Neuroscience(all)

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