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

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

Xiaobo Bai, Eva P Karasmanis and Elias T Spiliotis
Molecular biology of the cell, v 27(6), pp 897-906
15 Mar 2016
PMID: 26823018
url
https://doi.org/10.1091/mbc.E15-07-0493View
Published, Version of Record (VoR) Open

Abstract

Hippocampus - embryology Humans Receptors, N-Methyl-D-Aspartate - metabolism Rats Kinesin - chemistry Kinesin - metabolism Hippocampus - metabolism Microtubules - metabolism Animals Dogs HEK293 Cells Protein Conformation Membrane Proteins - metabolism Mice Neurons - metabolism Septins - metabolism Adaptor Proteins, Signal Transducing - metabolism Binding Sites
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.

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Cell Biology
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