Alternative titles; symbols
HGNC Approved Gene Symbol: CNIH2
Cytogenetic location: 11q13.2 Genomic coordinates (GRCh38): 11:66,278,175-66,284,206 (from NCBI)
In a search for genes specifically expressed in the embryonic hindbrain and pharyngeal areas of the developing mouse, Hoshino et al. (2007) identified Cnih2, which they designated Cnil, as a homolog of the Drosophila cni gene. The Drosophila cni gene is necessary for the transport of a TGF-alpha homolog, Gurken, to sites in the endoplasmic reticulum and promotes its incorporation into coat protein complex II (COPII) vesicles (Bokel et al., 2006). Like Drosophila cni, the deduced CNIH2 proteins in mouse, human, and chicken contain 3 putative transmembrane domains and a predicted C-terminal cytoplasmic COPII-interacting domain; unlike Drosophila cni, they all contain a highly conserved 16-amino acid sequence. Both the human and mouse proteins contain 160 amino acids.
For technical reasons, Hoshino et al. (2007) studied the function of CNIH2 in chicken. The expression patterns of CNIH2 in the developing chick showed temporal and spatial restriction to rhombomeres r3 and r5. HBEGF (126150), the heparin-binding epidermal growth factor, is also expressed in r3 and r5. Hoshino et al. (2007) showed that in cell culture CNIH2 expression facilitated the secretion of HBEGF, a ligand of ERBB4 (600543). Injection of a truncated form of CNIH2 that lacked the predicted C-terminal cytoplasmic loop into chick embryos resulted in disruption of the normal distribution of cranial neural crest cells (NCCs), which, in turn, caused abnormal fiber connections between cranial sensory ganglia. Knockdown of CNIH2 or HBEGF with siRNA produced a similar phenotype, which is also similar to that seen in ErbB4 knockout mice. Hoshino et al. (2007) concluded that CNIH2 acts to limit the site of HBEGF action to r3 and r5 and is essential for proper development of cranial nerves.
Schwenk et al. (2009) demonstrated by proteomic analysis that the majority of AMPA receptors (see 138248) in the rat brain are coassembled with 2 members of the cornichon family of transmembrane proteins, rather than with the transmembrane AMPA receptor regulatory proteins (TARPs). Coassembly with cornichon homologs 2 (CNIH2) and 3 (CNIH3) affects AMPA receptors in 2 ways: cornichons increase surface expression of AMPA receptors, and they alter channel gating by markedly slowing deactivation and desensitization kinetics. Schwenk et al. (2009) concluded that their results demonstrated that cornichons are intrinsic auxiliary subunits of native AMPA receptors and provide molecular determinants for glutamatergic neurotransmission in the central nervous system.
Scott (2007) mapped the CNIH2 gene to chromosome 11q13.1 based on an alignment of the CNIH2 sequence (GenBank BC047953) with the genomic sequence (build 36.2).
Bokel, C., Dass, S., Wilsch-Brauninger, M., Roth, S. Drosophila cornichon acts as cargo receptor for ER export of the TGF-alpha-like growth factor gurken. Development 133: 459-470, 2006. [PubMed: 16396907] [Full Text: https://doi.org/10.1242/dev.02219]
Hoshino, H., Uchida, T., Otsuki, T., Kawamoto, S., Okubo, K., Takeichi, M., Chisaka, O. Cornichon-like protein facilitates secretion of HB-EGF and regulates proper development of cranial nerves. Molec. Biol. Cell 18: 1143-1152, 2007. [PubMed: 17229890] [Full Text: https://doi.org/10.1091/mbc.e06-08-0733]
Schwenk, J., Harmel, N., Zolles, G., Bildl, W., Kulik, A., Heimrich, B., Chisaka, O., Jonas, P., Schulte, U., Fakler, B., Klocker, N. Functional proteomics identify cornichon proteins as auxiliary subunits of AMPA receptors. Science 323: 1313-1319, 2009. [PubMed: 19265014] [Full Text: https://doi.org/10.1126/science.1167852]
Scott, A. F. Personal Communication. Baltimore, Md. 7/18/2007.