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)

Liprin-alpha/SYD-2 is a multimodular scaffolding protein important for presynaptic differentiation and postsynaptic targeting of alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid glutamate receptors. However, the molecular mechanisms underlying these functions remain largely unknown. Here we report that liprin-alpha interacts with the neuron-specific kinesin motor KIF1A. KIF1A colocalizes with liprin-alpha in various subcellular regions of neurons. KIF1A coaccumulates with liprin-alpha in ligated sciatic nerves. KIF1A cofractionates and coimmunopreciptates with liprin-alpha and various liprin-alpha-associated membrane, signaling, and scaffolding proteins including alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptors, GRIP/ABP, RIM, GIT1, and beta PIX. These results suggest that liprin-alpha functions as a KIF1A receptor, linking KIF1A to various liprin-alpha-associated proteins for their transport in neurons.
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PMID:Association of the kinesin motor KIF1A with the multimodular protein liprin-alpha. 1252 3

Human PPFIA1 (also known as LIP.1 or Liprin alpha1) gene, located within CCND1-FGF4-EMS1 amplicon at human chromosome 11q13.3, encodes KIF1A-binding protein, which is implicated in trafficking of LAR subfamily PTPases and AMPA-type glutamate receptors. Human PPFIA4 (AF034801) and rat Ppfia4 (AY057064) are 5'-truncated partial cDNAs, and the complete coding sequence of PPFIA4 ortholog of any species remained to be identified. Here, we determined the complete coding sequence of human PPFIA4 gene by using bioinformatics. Exons 1-12 of PPFIA4 gene were located within human genome sequence AC096632.3, while exons 11-29 within AL451082.6. PPFIA4-MYOG locus (human chromosome 1q32.1) was paralogous to PPFIA2-LIN7A-MYF5-MYF6 locus (12q21.31), which was also paralogous to PPFIA3-LIN7B locus (19q13.41). PPFIA4 (1186 aa) showed 70.9%, 67.1%, and 61.8% total-amino-acid identity with PPFIA2, PPFIA1, and PPFIA3, respectively. PPFIA family members consist of PFIH1, PFIH2, PFIH3, PFIH4 domains and three SAM (Sterile alpha motif) domains. C-terminal binding domain for GRIP proteins (VRTYSC motif) was present in PPFIA1, PPFIA2 and PPFIA3, but not in PPFIA4. Bipartite nuclear localization signal was included within PFIH4 domain. PFIH2 domain was identical to ERM or Smc domain. The region spanning PFIH2-PFIH3 domains is the binding domain for KIF1A. The region spanning SAM1-SAM3 domains is the binding domain for LAR subfamily PTPases and PPFIBP (Liprin beta) family proteins. This is the first report on comprehensive characterization of PPFIA4 belonging to the PPFIA family of kinesin-cargo linkers.
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PMID:Identification and characterization of human PPFIA4 gene in silico. 1461 82

The function of the multi-PDZ domain scaffold protein GRIP1 (glutamate receptor interacting protein 1) in neurons is unclear. To explore the function of GRIP1 in hippocampal neurons, we used RNA interference (RNAi) to knock down the expression of GRIP1. Knockdown of GRIP1 by small interfering RNA (siRNA) in cultured hippocampal neurons caused a loss of dendrites, associated with mislocalization of the GRIP-interacting proteins GIuR2 (AMPA receptor subunit), EphB2 (receptor tyrosine kinase) and KIF5 (also known as kinesin 1; microtubule motor). The loss of dendrites by GRIP1-siRNA was rescued by overexpression of the extracellular domain of EphB2, and was phenocopied by overexpression of the intracellular domain of EphB2 and extracellular application of ephrinB-Fc fusion proteins. Neurons from EphB1-EphB2-EphB3 triple knockout mice showed abnormal dendrite morphogenesis. Disruption of the KIF5-GRIP1 interaction inhibited EphB2 trafficking and strongly impaired dendritic growth. These results indicate an important role for GRIP1 in dendrite morphogenesis by serving as an adaptor protein for kinesin-dependent transport of EphB receptors to dendrites.
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PMID:GRIP1 controls dendrite morphogenesis by regulating EphB receptor trafficking. 1596 73

Influenza A is a rapidly evolving virus that is successful in provoking periodic epidemics and occasional pandemics in humans. Viral assembly is complex as the virus incorporates an eight-partite genome of RNA (in the form of viral ribonucleoproteins, vRNPs), and viral genome assembly - with its implications to public health - is not completely understood. It has previously been reported that vRNPs are transported to the cell surface on Rab11-containing vesicles by using microtubules but, so far, no molecular motor has been assigned to the process. Here, we have identified KIF13A, a member of the kinesin-3 family, as the first molecular motor to efficiently transport vRNP-Rab11 vesicles during infection with influenza A. Depletion of KIF13A resulted in reduced viral titers and less accumulation of vRNPs at the cell surface, without interfering with the levels of other viral proteins at sites of viral assembly. In addition, when overexpressed and following two separate approaches to displace vRNP-Rab11 vesicles, KIF13A increased levels of vRNP at the plasma membrane. Together, our results show that KIF13A plays an important role in the transport of influenza A vRNPs, a crucial step for viral assembly.This article has an associated First Person interview with the first author of the paper.
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PMID:KIF13A mediates trafficking of influenza A virus ribonucleoproteins. 2906 83

The influenza virus is one of the major public health threats. However, the development of efficient vaccines and therapeutic drugs to combat this virus is greatly limited by its frequent genetic mutations. Because of this, targeting the host factors required for influenza virus replication may be a more effective strategy for inhibiting a broader spectrum of variants. Here, we demonstrated that inhibition of a motor protein kinesin family member 18A (KIF18A) suppresses the replication of the influenza A virus (IAV). The expression of KIF18A in host cells was increased following IAV infection. Intriguingly, treatment with the selective and ATP-competitive mitotic kinesin KIF18A inhibitor BTB-1 substantially decreased the expression of viral RNAs and proteins, and the production of infectious viral particles, while overexpression of KIF18A enhanced the replication of IAV. Importantly, BTB-1 treatment attenuated the activation of AKT, p38 MAPK, SAPK and Ran-binding protein 3 (RanBP3), which led to the prevention of the nuclear export of viral ribonucleoprotein complexes. Notably, administration of BTB-1 greatly improved the viability of IAV-infected mice. Collectively, our results unveiled a beneficial role of KIF18A in IAV replication, and thus, KIF18A could be a potential therapeutic target for the control of IAV infection.
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PMID:Selective and ATP-competitive kinesin KIF18A inhibitor suppresses the replication of influenza A virus. 3225 33