title: Septin 9 interacts with kinesin KIF17 and interferes with the mechanism of NMDA receptor cargo binding and transport.
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.
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA 19104.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA 19104.
authors.forename: Eva P
authors.initials: EP
authors.lastname: Karasmanis
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA 19104 ets33@drexel.edu.
authors.forename: Elias T
authors.initials: ET
authors.lastname: Spiliotis
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D004285:Dogs; D057809:HEK293 Cells; D006624:Hippocampus / Q000196:embryology / Q000378:metabolism; D006801:Humans; D016547:Kinesins / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D011487:Protein Conformation; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D058112:Septins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C513071:Apba1 protein, rat; C485813:KIF17 protein, human; D008565:Membrane Proteins; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; C119785:Septin9 protein, rat; C000613396:KIF17 protein, rat; C474315:SEPTIN9 protein, human; D058112:Septins; D016547:Kinesins
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