Septin 9 interacts with kinesin KIF17 and interferes with the mechanism of NMDA receptor cargo binding and transport

被引:31
作者
Bai, Xiaobo [1 ]
Karasmanis, Eva P. [1 ]
Spiliotis, Elias T. [1 ]
机构
[1] Drexel Univ, Dept Biol, Philadelphia, PA 19104 USA
基金
美国国家卫生研究院;
关键词
MOTOR PROTEIN KIF17; MAMMALIAN SEPTIN; SCAFFOLDING PROTEINS; HIPPOCAMPAL-NEURONS; VESICLE TRANSPORT; MICROTUBULES; DYNAMICS; SUBUNIT; AUTOINHIBITION; MORPHOGENESIS;
D O I
10.1091/mbc.E15-07-0493
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Intracellular transport involves the regulation of microtubule motor interactions with cargo, but the underlying mechanisms are not well understood. Septins are membrane- and microtubule-binding proteins that assemble into filamentous, scaffold-like structures. Septins are implicated in microtubule-dependent transport, but their roles are unknown. Here we describe a novel interaction between KIF17, a kinesin 2 family motor, and septin 9 (SEPT9). We show that SEPT9 associates directly with the C-terminal tail of KIF17 and interacts preferentially with the extended cargo-binding conformation of KIF17. In developing rat hippocampal neurons, SEPT9 partially colocalizes and comigrates with KIF17. We show that SEPT9 interacts with the KIF17 tail domain that associates with mLin-10/Mint1, a cargo adaptor/scaffold protein, which underlies the mechanism of KIF17 binding to the NMDA receptor subunit 2B (NR2B). Significantly, SEPT9 interferes with binding of the PDZ1 domain of mLin-10/Mint1 to KIF17 and thereby down-regulates NR2B transport into the dendrites of hippocampal neurons. Measurements of KIF17 motility in live neurons show that SEPT9 does not affect the microtubule-dependent motility of KIF17. These results provide the first evidence of an interaction between septins and a nonmitotic kinesin and suggest that SEPT9 modulates the interactions of KIF17 with membrane cargo.
引用
收藏
页码:897 / 906
页数:10
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