Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.4.4 (kinesin)
 5,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

KIF17, a recently characterized member of the kinesin superfamily proteins, has been proposed to bind in vitro to a protein complex containing mLin10 (Mint1/X11) and the NR2B subunit of the NMDA receptors (NMDARs). In the mammalian brain, NMDARs play an important role in synaptic plasticity, learning, and memory. Here we present, for the first time, the dynamic properties of KIF17 and provide evidence of its function in the transport of NR2B in living mammalian neurons. KIF17 vesicles enter and move specifically along dendrites in a processive way, at an average speed of 0.76 microm/sec. These vesicles are effectively associated with extrasynaptic NR2B, and thus they transport and deliver NR2B subunits in dendrites. However, KIF17 does not seem to enter directly into postsynaptic regions. Cellular knockdown or functional blockade of KIF17 significantly impairs NR2B expression and its synaptic localization. Interestingly, the decrease in the number of synaptic NR2B subunits is followed by a parallel increase in the number of NR2A subunits at synapses. In contrast, upregulation of the expression level of NR2B, after treatment with the NMDAR antagonist D(-)-2-amino-5-phosphonopentanoic acid, simultaneously increases the expression level of KIF17. These observations concerning the downregulation or upregulation of KIF17 and NR2B reveal the probable existence of a shared regulation process between the motor and its cargo. Taken together, these results illustrate the complex mechanisms underlying the active transport and regulation of NR2B by the molecular motor KIF17 in living hippocampal neurons.
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PMID:KIF17 dynamics and regulation of NR2B trafficking in hippocampal neurons. 1251 9

Establishment and maintenance of cell structures and functions are highly dependent on the efficient regulation of intracellular transport in which proteins of the kinesin superfamily (KIFs) are very important. In this regard, how KIFs regulate the release of their cargo is a critical process that remains to be elucidated. To address this specific question, we have investigated the mechanism behind the regulation of the KIF17-Mint1 interaction. Here we report that the tail region of the molecular motor KIF17 is regulated by phosphorylation. Using direct visualization of protein-protein interaction by FRET and various in vitro and in vivo approaches we have demonstrated that CaMKII-dependent phosphorylation of KIF17 on Ser 1029 disrupts the KIF17-Mint1 association and results in the release of the transported cargo from its microtubule-based transport.
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PMID:Disruption of KIF17-Mint1 interaction by CaMKII-dependent phosphorylation: a molecular model of kinesin-cargo release. 1817 23

Amyloid-beta protein precursor (AbetaPP) is a receptor-like, type-I membrane protein that plays a central role in the pathogenesis of Alzheimer's disease. The cytoplasmic domain of AbetaPP is important for the metabolism and physiological functions of AbetaPP and contains a GYENPTY motif that interacts with proteins that contain a phosphotyrosine binding (PTB) domain such as X11/Mint, FE65, and the JIP family of proteins. X11 and X11-like proteins are neuronal adaptor proteins involved in presynaptic function and the intracellular trafficking of proteins. Recent studies in X11s knockout mice confirmed findings from in vitro studies that X11 proteins affect AbetaPP metabolism and the generation of amyloid-beta peptide. FE65 proteins are involved in transactivation in coordination with the intracellular domain fragment of AbetaPP, and/or in cellular responses to DNA damage. Neurodevelopmental defects observed in FE65s double knockout mice suggest that FE65 proteins cooperate with AbetaPP to play a role in neuronal cytoskeletal regulation. c-Jun N-terminal kinase (JNK) interacting protein-1 (JIP-1), a scaffolding protein for the JNK kinase cascade, has been suggested to mediate the intracellular trafficking of AbetaPP by molecular motor kinesin-1. This article reviews some of the recent findings regarding the regulation of physiological function and metabolism of AbetaPP by AbetaPP binding proteins.
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PMID:Regulation of the physiological function and metabolism of AbetaPP by AbetaPP binding proteins. 1958 34

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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PMID:Septin 9 interacts with kinesin KIF17 and interferes with the mechanism of NMDA receptor cargo binding and transport. 2682 18