Disease relevance of CNGA1

• Here we narrow the achromatopsia locus to 1.4 cM and show that Pingelapese achromatopsia segregates with a missense mutation at a highly conserved site in CNGB3, a new gene that encodes the beta-subunit of the cone cyclic nucleotide-gated cation channel [1].
• Treatment of human glioma cell T98 with thyroid hormone T(3) caused a significant increase in anti-CNG1 expression and a parallel decrease in sense CNG(alpha)1 expression [2].

High impact information on CNGA1

• The human cGMP-gated channel gene (CNCG) is located on chromosome 4 and contains at least 10 exons [3].
• Ca2+/CaM also binds the N-terminal region of CNGB1 subunits and disrupts an intersubunit, N- and C-terminal interaction between CNGB1 and CNGA1 subunits in rod channels [4].
• Comparison of expression patterns between adult and fetal cerebral cortex revealed that there were concurrent developmental changes in the expression levels of anti-CNG1 and CNG(alpha)1 [2].
• The mouse channel gene locus (Cncg) was mapped by interspecific backcross haplotype analysis 0.9 centimorgan proximal of the Kit locus on chromosome 5 [5].
• When applied to the intracellular side of inside-out excised patches from Xenopus oocytes, dequalinium blocks CNGA1 channels with a K(1/2) approximately 190 nM and CNGA1+CNGB1 channels with a K(1/2) approximately 385 nM, at 0 mV [6].

Biological context of CNGA1

• The mutant allele of CNGA1 itself shows linkage to the disease with maximum lod score of 4.43 at theta;=0 [7].
• The distinct temporal patterns of expression of these components of cGMP signaling pathways suggest different physiological roles for sGC, PKG-I, and CNG-1 in spermiogenesis and steroidogenesis [8].
• PURPOSE: The cyclic nucleotide gated cation channel subunit, CNGA3, (also known as the cone alpha CNG subunit), plays a vital role in signal transduction of human cone cells [9].
• With the aim of understanding the relation between structure and gating of CNGA1 channels from bovine rod, an extensive cysteine scanning mutagenesis was performed [10].
• The exon/intron organization (location and length of exons and introns) of the cCNCG1 gene is very similar to that of the human rod photoreceptor cGMP-gated cation channel alpha-subunit gene [11].

Anatomical context of CNGA1

• Previous studies have identified the expression of CNGA1 channels in vascular endothelial cells [12].
• In the absence of CNGB1, only trace amounts of the CNGA1 subunit were found on the rod outer segment [13].
• Molecular cloning of cyclic nucleotide-gated cation channel subunits from rat pineal gland [14].
• These results demonstrate that sGC, PKG-I, and CNG-1 are expressed in a stage- and cell-specific manner in the rat testis [8].
• In contrast to sGC and PKG-I, CNG-1 was expressed only in cytoplasm and the residual bodies of late-stage (17-19) spermatids, with no staining observed in blood vessels and Leydig cells [8].

Associations of CNGA1 with chemical compounds

• Dequalinium has recently been reported to block CNGA1 and CNGA2 channels expressed in Xenopus laevis [15].
• Three types of subunits have been cloned: an alpha-subunit (CNG1), two beta-subunit splice variants (rCNG4.1 and rCNG4.2) and a hydrophilic glutamic acid-rich protein (rGARP) [14].
• In this study, we investigated the structure and rearrangement of the CNGA1 channel pore using cysteine mutations and cysteine-specific modification [16].

Other interactions of CNGA1

• Autosomal recessive retinitis pigmentosa in a Pakistani family mapped to CNGA1 with identification of a novel mutation [7].
• Cysteine residues were also not critical for the formation of NCKX2 homo-oligmers or NCKX2 hetero-oligomers with the CNGA subunit of the cGMP-gated channel [17].
• These efforts have resulted in the isolation of olfactory-specific forms of a G protein, an adenylyl cyclase, and a cyclic nucleotide-gated cation channel [18].

Analytical, diagnostic and therapeutic context of CNGA1

• In situ hybridization with sections of rat brain revealed the co-expression of CNG1, CNG4 and GARP in pinealocytes [14].
• Furthermore, RT-PCR analyses showed specific gene expression of both cGMP-phosphodiesterase beta-subunit and cone-type cGMP-gated cation channel alpha-subunit in this region [19].
• Using annotated GenBank sequences, BLAST searches of unfinished sequences and degenerate oligonucleotide polymerase chain reaction (PCR) screens, we have identified and compiled genes for 38 C. elegans potassium channel and two cyclic nucleotide-gated cation channel subunits, representing eight conserved multigene families [20].

References