The Atypical Kinesin KIF26A Facilitates Termination of Nociceptive Responses by Sequestering Focal Adhesion Kinase.

• 发表时间: 09 2018 11
• 来源期刊: Cell Rep
• DOI: 10.1016/j.celrep.2018.05.075
• PMID: 30208315
• 文章类型: Journal Article
• 作者列表: Wang L,Tanaka Y,Wang D,Morikawa M,Zhou R,Homma N,Miyamoto Y,Hirokawa N

关键词: Ca homeostasis; KIF26A; focal adhesion kinase; integrin; kinesin; mouse model; nociceptive response; plasma membrane Ca ATPase; prolonged pain; sensory neurons

Mesh: Animals; Axons / metabolism; Calcium / metabolism; Focal Adhesion Protein-Tyrosine Kinases / genetics metabolism; Hyperalgesia / metabolism; Kinesins / genetics metabolism; Male; Mice; Mice, Knockout; Microtubules / metabolism; Nociceptors / metabolism; Peripheral Nerves / cytology; Phosphorylation; Signal Transduction / genetics physiology

Abstract

Kinesin superfamily proteins (KIFs) are molecular motors that typically alter the subcellular localization of their cargos. However, the atypical kinesin KIF26A does not serve as a motor but can bind microtubules and affect cellular signaling cascades. Here, we show that KIF26A maintains intracellular calcium homeostasis and negatively regulates nociceptive sensation. Kif26a-/- mice exhibit intense and prolonged nociceptive responses. In their primary sensory neurons, excessive inhibitory phosphorylation of plasma membrane Ca2+ ATPase (PMCA) mediated by focal adhesion kinase (FAK) rendered the Ca transients resistant to termination, and the peripheral axonal outgrowth was significantly enhanced. Upstream, KIF26A is directly associated with a FERM domain of FAK and antagonizes FAK function in integrin-Src family kinase (SFK)-FAK signaling, possibly through steric hindrance and localization to cytoplasmic microtubules.