Disease relevance of KLC1

• Using the yeast two-hybrid assay, we found that PC2 interacts with the microtubule-dependent motor kinesin-2 subunit KIF3A, a protein involved in polycystic kidney disease [1].
• Association of the herpes simplex virus type 1 Us11 gene product with the cellular kinesin light-chain-related protein PAT1 results in the redistribution of both polypeptides [2].
• Kinesin light chain in a eubacterium [3].
• A eubacterial homolog of a kinesin light chain gene has been isolated and characterized from the cyanobacterium Plectonema boryanum [3].

Psychiatry related information on KLC1

• We hypothesized that kinesin light-chain dysfunction might be involved in the pathogenesis of Alzheimer's disease (AD) [4].
• Here, we show that tumor necrosis factor impairs kinesin motor activity and hyperphosphorylates kinesin light chain through activation of two putative kinesin light chain kinases [5].

High impact information on KLC1

• Coimmunoprecipitation, sucrose gradient, and direct in vitro binding demonstrated that APP forms a complex with the microtubule motor, conventional kinesin (kinesin-I), by binding directly to the TPR domain of the kinesin light chain (KLC) subunit [6].
• Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I [6].
• In addition, in the inactive state, the KHC motor domains are pushed apart by the KLC subunit [7].
• We show here that Alcalpha strongly associates with kinesin light chain (K(D) approximately 4-8 x 10(-9) M) through a novel tryptophan- and aspartic acid-containing sequence [8].
• Inactivation of kinesin, hyperphosphorylation of kinesin light chain, and perinuclear clustering of mitochondria exhibit the same p38 mitogen-activated kinase dependence, indicating their functional relationship [5].

Biological context of KLC1

• To assess the physiological relevance of an allelic variation in the KNS2 gene, the association analysis of three single nucleotide polymorphisms (SNPs) in the 5'UTR or in intronic sequences of KNS2 gene were performed in 100 AD brain patients and in 103 controls [4].
• The major binding site for kinesin light chain in kinesin heavy chain was mapped to residues 789-813 at the C-terminal end of the heavy chain stalk domain [9].
• A scaffold protein JIP-1b enhances amyloid precursor protein phosphorylation by JNK and its association with kinesin light chain 1 [10].
• The carboxyl-terminal dsRNA-binding domain of Us11, which also contains the nucleolar retention and nuclear export signals, binds PAT1, whereas 149 residues derived from the KLC homology region of PAT1 are important for binding to Us11 [2].
• Alternative splicing of kinesin light chain pre-mRNA has been observed in lower organisms, although evidence for alternative splicing of the human gene has not been reported [11].

Anatomical context of KLC1

• AbetaPP processing also occurs in nerve processes where AbetaPP is transported from the cell body by kinesin-I, a microtubule motor composed of two kinesin heavy chain and two kinesin light chain (Klc) subunits [12].
• Kinesin heavy chain (HC) was expressed in COS cells either alone or with kinesin light chain (LC) [13].
• Subcellular fractionation of adult rat brain revealed torsinA and KLC associated with cofractionating membranes, and both proteins were co-immunoprecipitated after cross-linking cytoplasmically oriented proteins on isolated rat brain membranes [14].
• Analysis of Kinesin-2 Function in Photoreceptor Cells Using Synchronous Cre-loxP Knockout of Kif3a with RHO-Cre [15].
• Tumor necrosis factor induces hyperphosphorylation of kinesin light chain and inhibits kinesin-mediated transport of mitochondria [5].

Associations of KLC1 with chemical compounds

• The phosphotyrosine binding domain of JIP1 binds the cytoplasmic tail of AbetaPP, whereas the JIP1 C-terminal region interacts with the tetratrico-peptide repeats of Klc1 [12].
• The interaction of HAP1 with kinesin light chain is demonstrated via a yeast two-hybrid assay, glutathione S-transferase pull down, and coimmunoprecipitation [16].
• In the presence of citrate, this step is followed by formation of an intermediate complex with monoferric ovotransferrin; stability constant KLC = (0.435 +/- 0.015) mM [17].
• We describe a patient with KLC who had the typical features of this disease and responded partially to treatment with oral isotretinoin [18].
• We describe a 35-year-old woman with KLC who had the typical features of widespread violaceous, reticulate, and striae-like eruptions with a prominent keratotic component over a nine-year period and who responded well to treatment with calcipotriol ointment [19].

Physical interactions of KLC1

• Co-immunoprecipitation and confocal imaging strategies further showed that GRIF-1 can bind to the tetrameric kinesin light-chain/kinesin heavy-chain complex [20].

Other interactions of KLC1

• Amyloid beta protein precursor (AbetaPP), but not AbetaPP-like protein 2, is bridged to the kinesin light chain by the scaffold protein JNK-interacting protein 1 [12].
• No synergistic effects were found between the APOE epsilon 4 allele and KNS2 gene polymorphisms [4].
• We also show that JIP1 does not bridge the AbetaPP gene family member AbetaPP-like protein 2, APLP2, to Klc1 [12].
• PAT1 shows homology to kinesin light chain, which is a component of the plus-end directed microtubule-based motor involved in transporting membrane proteins to the basolateral surface [21].
• JIP-1b also enhanced the association of kinesin light chain 1 with APP [10].

Analytical, diagnostic and therapeutic context of KLC1

• To assess the selectivity of kinesin light chain interaction with the heavy chains, we performed immunoprecipitation experiments [22].
• Immunofluorescence and biochemical subfractionation suggested differences in the subcellular localization of the two kinesin light chain gene products [22].
• In this study, torsinA was found to move in conjunction with vimentin in three cell culture paradigms-recovery from microtubule depolymerization, expression of a dominant-negative form of kinesin light chain and respreading after trypsinization [23].
• Localization of the human kinesin light chain gene (KNS2) to chromosome 14q32.3 by fluorescence in situ hybridization [24].
• On Western blots of total cell homogenates, it recognized a single KLC isoform, which copurified with mitochondria [25].

References