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

Mol Biol Cell. 2016 Mar 15;27(6):897-906. doi: 10.1091/mbc.E15-07-0493. Epub 2016 Jan 28.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

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

Substances

  • Adaptor Proteins, Signal Transducing
  • Apba1 protein, rat
  • KIF17 protein, human
  • Membrane Proteins
  • NR2B NMDA receptor
  • Receptors, N-Methyl-D-Aspartate
  • Septin9 protein, rat
  • KIF17 protein, rat
  • SEPTIN9 protein, human
  • Septins
  • Kinesins