Disease relevance of LPHN2

• Genomic structure and expression profile of LPHH1, a 7TM gene variably expressed in breast cancer cell lines [1].
• A phage lambda library prepared from genomic DNA of a tertiary Lec1 transfectant (3 degrees T) has now been used to obtain clones encoding an active GlcNAc-TI enzyme [2].
• alpha-N-Acetylglucosaminidase (EC 3.2.1.50) is a lysosomal enzyme that is deficient in the genetic disorder Sanfilippo syndrome type B. To study the human enzyme, we expressed its cDNA in Lec1 mutant Chinese hamster ovary (CHO) cells, which do not synthesize complex oligosaccharides [3].

High impact information on LPHN2

• The initial intercellular contact was most often evidenced by neutrophils rolling on the monolayer at a mean rate of congruent to 10 microns/s. Anti-E-selectin monoclonal antibody, CL2/6, inhibited this interaction by > 90% [4].
• This laboratory has previously identified a human gene encoding N-acetylglucosaminyltransferase I (GlcNAc-TI; EC 2.4.1.101) by complementation of the glycosylation defect in the Lec1 Chinese hamster ovary (CHO) cell mutant [2].
• A small genomic DNA fragment [approximately 4.6 kilobases (kb)], isolated from an Alupositive lambda clone, conferred human GlcNAc-TI activity upon transfection into Lec1 cells [2].
• Northern blot analysis with the same probe showed that Lec1 mutant cells also possessed an approximately 2.7-kb poly(A)+ RNA, indicating that the lec1 mutation is a point mutation [2].
• RP were then compared at three equivalent CL ranges: CL1, 850-600; CL2 599-460; CL3 459-280 [5].

Biological context of LPHN2

• 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 [6].
• Gene identification studies, centred on a region of overlapping loss of heterozygosity in breast tumours within band 1p31.1, lead to the characterisation of LPHH1, a novel human 7TM gene [1].
• The coding sequence of LPHH1 extends over a 60 kb region and comprises in excess of 28 exons [1].
• 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 [7].
• Aggrus on Lec1 cells induced platelet aggregation, but those on Lec2 and Lec8 cells did not [8].

Anatomical context of LPHN2

• Northern and RT-PCR analysis of a panel of tumour cell lines showed that LPHH1 expression was variable, apparently elevated in some lines and absent or markedly reduced in others [6].
• LPHH1 also appears to be downregulated in human bone marrow [1].
• 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) [9].
• 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 [10].
• Lec1 cells are very sensitive to lysis by beta-interferon treated human NK cells, but both parent and Lec4 cells are resistant to NK lysis [11].

Associations of LPHN2 with chemical compounds

• Due to a specific block in N-linked carbohydrate processing, Lec1 cells produce only high mannose-type oligosaccharides, but their glycolipids are identical to those of the parent [12].
• Swainsonine-treated parent cells are nearly as sensitive to natural killer lysis as the Lec1 mutants [12].
• 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 [13].
• PGF2 alpha increased corticosterone in CL1, CL2 and CL3 [9].
• 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 [14].

Other interactions of LPHN2

• Co-immunoprecipitation of ProSAP1 and CIRL1 (but not CIRL2) from rat brain extracts indicates that this interaction also occurs in vivo in rat brain [15].
• We here show that loss of endoglin expression mediated by either antisense DNA or siRNA results in a direct perturbation of EMT and reduced expression of EMT markers including slug, runx2, RhoA, and latrophilin-2 [16].

Analytical, diagnostic and therapeutic context of LPHN2

• No somatic LPHH1 mutations were detected through sequence analysis of four primary breast tumours that showed loss of the adjacent 1p31.1 marker D1S207 [1].
• Using one of these monoclonal antibodies (CL2) an indirect antigen capture ELISA was developed for the detection of soluble antigen [17].
• A direct immunofluorescence technique was developed using FITC conjugates of anti-listeria antibodies (CL2 and CL17) [17].

References