Alternative titles; symbols
HGNC Approved Gene Symbol: ZACN
Cytogenetic location: 17q25.1 Genomic coordinates (GRCh38): 17:76,079,182-76,082,806 (from NCBI)
LGICZ1 is a zinc-activated ligand-gated ion channel that defines a new subgroup of the cysteine-loop superfamily of ligand-gated ion channels (Davies et al., 2003).
By database analysis using a consensus sequence of conserved ligand-gated ion channel motifs as probe, followed by PCR of human fetal brain and spinal cord cDNA libraries, Davies et al. (2003) cloned LGICZ1, which they called ZAC. The deduced 411-amino acid protein contains a signal sequence, a cys-cys motif, 4 transmembrane domains, and several invariant residues consistent with the conserved secondary structure of the cysteine-loop superfamily; however, LGICZ1 is not closely related to any known subunit of this superfamily. Rodent genomes lack a functional Lgicz1 gene, but the canine genome contains a functional gene that shares 84% identity with LGICZ1. RT-PCR of human tissues detected expression in prostate, thyroid, trachea, fetal brain, spinal cord, placenta, and stomach. No expression was detected in adult whole brain, heart, liver, spleen, or kidney. Northern blot analysis detected a 1.5-kb transcript in placenta and stomach.
By database analysis, followed by RT-PCR of human brain RNA, Houtani et al. (2005) cloned LGICZ1, which they called L2, and isolated 2 splice variants. They identified 4 N-glycosylation sites. Nested PCR analysis detected expression in human pancreas, brain, liver, lung, heart, kidney, and skeletal muscle, but not placenta. In situ hybridization of brain regions detected LGICZ1 expression in the hippocampus, striatum, and thalamus. Immunofluorescence studies localized LGICZ1 to the cell membrane and surfaces of cellular processes. Western analysis and glycopeptidase treatment of subcellular fractions localized LGICZ1 to the membrane fraction and showed that it undergoes N-glycosylation. Immunolocalization of human brain tissues detected LGICZ1 protein in CA3 pyramidal cells in the hippocampus and some granule and polymorphic layer cells of the dentate gyrus.
Using whole-cell patch-clamp analysis, Davies et al. (2003) showed that LGICZ1 expressed in HEK cells displayed spontaneous current and concluded that LGICZ1 subunits form channels that can open in the absence of agonist. Addition of Zn(2+) caused activation of an inward current in a concentration-dependent manner, while agonists of other ligand-gated ion channels had no effect. By varying intracellular K(+) concentration, the authors identified a shift in LGICZ1 channel activity and concluded that K(+) ions play a role in zinc-activated current. Davies et al. (2003) compared spontaneous LGICZ1 channel activation kinetics with zinc-activated channels and suggested that Zn(2+) activates LGICZ1 channels that are closed prior to its addition.
Davies et al. (2003) determined that the LGICZ1 gene contains 9 exons. Houtani et al. (2005) identified 2 splice variants: 1 variant comprises exons 4 to 6 with a partial deletion of exon 7, and the other variant comprises 5 of the first 7 exons lacking exons 3 and 4.
By genomic sequence analysis, Davies et al. (2003) mapped the LGICZ1 gene to chromosome 17q23.
Houtani et al. (2005) mapped the LGICZ1 gene to chromosome 17q25.3 downstream of the GALR2 (603691) and in complementary sequence to the 3-prime noncoding region of EXOC7 (608163).
Davies, P. A., Wang, W., Hales, T. G., Kirkness, E. F. A novel class of ligand-gated ion channel is activated by Zn(2+). J. Biol. Chem. 278: 712-717, 2003. [PubMed: 12381728] [Full Text: https://doi.org/10.1074/jbc.M208814200]
Houtani, T., Munemoto, Y., Kase, M., Sakuma, S., Tsutsumi, T., Sugimoto, T. Cloning and expression of ligand-gated ion-channel receptor L2 in central nervous system. Biochem. Biophys. Res. Commun. 335: 277-285, 2005. [PubMed: 16083862] [Full Text: https://doi.org/10.1016/j.bbrc.2005.07.079]