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)

Insulin induces translocation of the glucose transporter GLUT4 from intracellular storage compartment to the plasma membrane via complex mechanisms that require intact cytoskeletal networks. In cultured adipocytes, conventional kinesin motor proteins have been proposed to mediate GLUT4 movements on microtubules. It remains, however, unclear whether kinesin motor system plays a similar regulatory role in myocytes. We addressed this issue using C2C12 myoblasts, which have now been shown to express both heavy and light chains of conventional kinesin. In these cells, overexpression of either wild-type kinesin light chain 2 (KLC2) or its phosphorylation-defective mutant did not significantly affect insulin-stimulated translocation of exofacial Myc-tagged GLUT4-green fluorescent protein to the cell surface and its subsequent externalization. Likewise, a dominant-negative mutant of KLC2 had no marked effect on GLUT4 movements in this cell type. These results suggest that conventional kinesin is dispensable for insulin-induced GLUT4 translocation in cultured myoblasts and may thus reveal a cell-type specific role of the microtubules-based cytoskeleton in glucose transport in response to insulin.
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PMID:Insulin-induced GLUT4 movements in C2C12 myoblasts: evidence against a role of conventional kinesin motor proteins. 1877 5

Lithium has been the gold standard in the treatment of bipolar disorder (BPD) for 60 y. Like lithium, glycogen synthase kinase 3 (GSK-3) inhibitors display both antimanic-like and antidepressant-like effects in some animal models. However, the molecular mechanisms of both lithium and GSK-3 inhibitors remain unclear. Here we show that the GSK-3 inhibitor AR-A014418 regulated alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA)-induced GluR1 and GluR2 internalization via phosphorylation of kinesin light chain 2 (KLC2), the key molecule of the kinesin cargo delivery system. Specifically, AMPA stimulation triggered serine phosphorylation of KLC2 and, subsequently, the dissociation of the GluR1/KLC2 protein complex. This suggests that GSK-3 phosphorylation of KLC2 led to the dissociation of AMPA-containing vesicles from the kinesin cargo system. The peptide TAT-KLCpCDK, a specific inhibitor for KLC2 phosphorylation by GSK-3beta, reduced the formation of long-term depression. Furthermore, the TAT-KLCpCDK peptide showed antimanic-like effects similar to lithium's on amphetamine-induced hyperactivity, a frequently used animal model of mania. It also induced antidepressant-like effects in the tail suspension and forced swim tests, two commonly used animal models of depression. Taken together, the results demonstrated that KLC2 is a cellular target of GSK-3beta capable of regulating synaptic plasticity, particularly AMPA receptor trafficking, as well as mood-associated behaviors in animal models. The kinesin cargo system may provide valuable novel targets for the development of new therapeutics for mood disorders.
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PMID:A kinesin signaling complex mediates the ability of GSK-3beta to affect mood-associated behaviors. 2053 17

Kinesin-mediated cargo transport is required for many cellular functions and plays a key role in pathological processes. Structural information on how kinesins recognize their cargoes is required for a molecular understanding of this fundamental and ubiquitous process. Here, we present the crystal structure of the tetratricopeptide repeat domain of kinesin light chain 2 in complex with a cargo peptide harboring a "tryptophan-acidic" motif derived from SKIP (SifA-kinesin interacting protein), a critical host determinant in Salmonella pathogenesis and a regulator of lysosomal positioning. Structural data together with biophysical, biochemical, and cellular assays allow us to propose a framework for intracellular transport based on the binding by kinesin-1 of W-acidic cargo motifs through a combination of electrostatic interactions and sequence-specific elements, providing direct molecular evidence of the mechanisms for kinesin-1:cargo recognition.
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PMID:Structural basis for kinesin-1:cargo recognition. 2351 14