Disease relevance of LPHN1

• Isolation and characterization of a human homologue of the latrophilin gene from a region of 1p31.1 implicated in breast cancer [1].
• A 3.5-kb GFAP mRNA was detected in five of the ten glioma cell lines, one of which was U-251 MG cell line and the other four were clones derived from the same tumor (CL1, 2, 3, and 4) [2].
• MCF7 breast carcinoma cells and CL1 lung adenocarcinoma cells were both insensitive to gefitinib [3].
• EXPERIMENTAL DESIGN: Prostate cancer cell lines (LNCaP, LAPC4, CL1, and DU145) were treated with bortezomib and apoptotic stimuli (TRAIL, chemotherapy, and tumor necrosis factor alpha), alone or in combination [4].
• The proteomic profiles of a human hepatoma revertant, CL1, and its original cell line, SMMC7721, were compared by using an improved two-dimensional electrophoresis (2-DE) procedure, with multi-IPGstrips gels (length <or= 13 cm) run simultaneously on one sodium dodecyl sulfate (SDS) gel (shortened MSOG method) [5].

High impact information on LPHN1

• In stimulating exocytosis, alpha-latrotoxin binds to two distinct families of neuronal cell-surface receptors, neurexins and CLs (Cirl/latrophilins), which probably have a physiological function in synaptic cell adhesion [6].
• Consistent with this, CD4 synthesized by the Lec2 mutant, which does not add sialic acid to oligosaccharides, was identical to the glycoprotein produced by wild-type CHO cells [7].
• RP were then compared at three equivalent CL ranges: CL1, 850-600; CL2 599-460; CL3 459-280 [8].
• Topotecan efflux was inhibited and accumulation was partially restored in CL1/Tpt and MCF7/TPT cells when cells were incubated simultaneously with gefitinib [3].
• In contrast, these concentrations of gefitinib caused a dose-dependent reversal of resistance to paclitaxel in CL1/Pac cells, to doxorubicin in MCF7/ADR cells, and to topotecan in CL1/Tpt and MCF7/TPT cells [3].

Chemical compound and disease context of LPHN1

• RESULTS: Bortezomib induced cell death of androgen-dependent (LNCaP and LAPC4) and androgen-independent (CL1 and DU145) prostate cancer cell lines, although androgen-dependent cells were more sensitive to proteasome inhibition [4].
• Multiple forms of cyclohexanone oxygenase from Nocardia globerula CL1 [9].
• Cathepsin L1 (CL1), an immunogenic cysteine proteinase secreted by juvenile and adult Fasciola hepatica, was assessed for its potential as a diagnostic agent for the serologic detection of human fascioliasis [10].
• Here, we investigate the role of mGPDH in maintaining an increased rate of glycolysis and evaluate glycerophosphate-dependent ROS production in prostate cancer cell lines (LNCaP, DU145, PC3, and CL1) [11].

Biological context of LPHN1

• To explore the roles of glycosylation in sICAM-1 activity, we expressed sICAM-1 in mutant CHO cell lines differing in glycosylation, including Lec2, Lec8, and Lec1 as well as in CHO cells cultured in the presence of the alpha-mannosidase-I inhibitor kifunensine [12].
• Aggrus on Lec1 cells induced platelet aggregation, but those on Lec2 and Lec8 cells did not [13].
• The 4209 bp open reading frame of the 7 kb LPHH1 transcript encodes a peptide which shows approximately 65% identity to rat latrophilin, a G-coupled, seven span transmembrane protein, which binds alpha-latrotoxin [1].
• Remifentanil pharmacokinetics were best described by a two-compartment model with lean body mass as a significant covariate, where V1 = 0.129(lean body mass-50) + 3.79 l, V2 = 6.87 l, CL1 = 0.0389(lean body mass-50) + 2.34 l/min and CL2 = 1.14 l/min [14].
• Comparison of the CL1 and CL2 sequences from the 57.1, 8.1, 18.2 and 7.1 ancestral haplotypes revealed that the lengths of the elements vary, both between the duplicated loci within a haplotype and between haplotypes, apparently because certain sequences are inserted or deleted [15].

Anatomical context of LPHN1

• In situ hybridization revealed that ProSAP1 and CIRL1 are co-expressed in the cortex, hippocampus, and cerebellum [16].
• Follicles and CL were divided according to their different developmental stages; follicles: previtellogenic, early-vitellogenic, mid-vitellogenic and fully-grown; CL: CL1 (unshelled eggs in the oviducts), CL2 (shelled eggs in the oviducts), CL3 (eggs laid 6 h previously) and CL4 (eggs laid 48 h previously) [17].
• The interaction of T. rubrum with chinese hamster ovary epithelial cells and their glycosylation-deficient mutants demonstrated a higher adhesion index in Lec1 and Lec2 mutants, that express mannose and galactose, respectively [18].
• Examination of thin section by transmission electron microscopy showed that after fungal ingestion by Lec2 cells the fungi are enclosed in a 'loose'-type vacuole while the other cells are found within a 'tight'-type membrane-bound cytoplasmic vacuole [19].
• In this study we examine the effects of expression of a newly cloned Ca2+-independent receptor for alpha-Ltx (CIRL) on secretion from bovine chromaffin cells [20].

Associations of LPHN1 with chemical compounds

• Lec8 and Lec2 cells show an overall reduction of galactose and/or sialic acid in their glycoconjugates due to defects in the translocation of UDP-galactose and CMP-sialic acid, respectively [21].
• PGF2 alpha release was highest in CL4, and PGE2 in CL1 and CL2, corticosterone was highest in CL4 [17].
• PGF2 alpha increased corticosterone in CL1, CL2 and CL3 [17].
• SGnRH and SP decreased PGE2 and progesterone and increased PGF2 alpha by CL1 and CL2 [22].
• Addition of the carbohydrates methyl alpha-D-mannopyranoside and methyl alpha-D-galactopyranoside to the interaction medium, pretreatment of Lec1 and Lec2 cells with lectins Concanavalina A and Arachis hypogaea and pretreatment with sodium periodate decreased the adhesion and the endocytic index [19].

Other interactions of LPHN1

• However, the toxin induces pores efficiently in COS-7 cells transfected with the heptahelical receptor latrophilin or the monotopic receptor neurexin [23].
• On the other hand, latrophilin is a seven-transmembrane protein and belongs to the family of G-protein-coupled receptors [24].

Analytical, diagnostic and therapeutic context of LPHN1

• Pulsed field gel electrophoresis analysis shows that both CL1 and CL2 are in the central MHC and are about 16 kilobases apart [25].
• Most importantly, we observed a complete arrest of growth in CL1 and 22RV1 xenografts treated intratumorally with the diastereomer [26].
• Sequential affinity chromatography of glycopeptides derived from [3H]mannose-labeled LPHN and LPHN/O on lectin columns revealed similar patterns of N-linked glycosylation of both forms indicating that the presence of O-linked oligosaccharides did not affect or alter the processing of N-linked oligosaccharides [27].
• METHODS: The cell surface marker expression profiles of CL1 and LNCaP were examined using flow cytometry [28].
• Markedly differential gene expression was confirmed using RT-PCR and further examined using immunohistochemistry among the prostate cancer cell lines LAPC-4, LNCaP, CL1, CL2, DU145, and PC-3 [28].

References