Kirrel2, also known as kin of irregular chiasm-like 2, belongs to the immunoglobulin superfamily. It contains five Ig domains, a transmembrane domain, and an intracellular domain. Kirrel2 is involved in multiple biological processes. In the pancreas, it is specifically expressed in beta-cells and may play a role in pancreas development or beta-cell function [2]. In the olfactory system, it is related to the targeting of axons in the olfactory bulb. In the kidney, it is associated with glomerular function as it encodes the slit diaphragm protein Neph3/filtrin [4,5].

Loss-of-function experiments in mice have revealed important roles of Kirrel2. In mice lacking Kirrel2, MOR174-9-and M72-expressing olfactory sensory neuron (OSN) axons projecting to the DII region of the olfactory bulb target ectopic glomeruli, indicating that Kirrel2 is required for axonal coalescence in subsets of OSNs that project to this region [1]. In pancreatic MIN6 cells and in mice with Kirrel2 genetic deletion, basal insulin secretion from β-cells increased, suggesting that Kirrel2 in pancreatic β-cells localizes to adherens junctions and regulates basal insulin secretion [3].

In summary, Kirrel2 is crucial for processes such as axonal targeting in the olfactory system and basal insulin secretion regulation in the pancreas. Gene-knockout mouse models have been instrumental in uncovering its functions in these areas, providing insights into potential mechanisms underlying related biological processes and disease conditions [1,3].

References:

1. Vaddadi, Neelima, Iversen, Katrine, Raja, Reesha, Dumontier, Emilie, Cloutier, Jean-François. 2019. Kirrel2 is differentially required in populations of olfactory sensory neurons for the targeting of axons in the olfactory bulb. In Development (Cambridge, England), 146, . doi:10.1242/dev.173310. https://pubmed.ncbi.nlm.nih.gov/31142543/

2. Sun, Chao, Kilburn, Daniel, Lukashin, Alex, Diefenbach, Beate, Carulli, John P. . Kirrel2, a novel immunoglobulin superfamily gene expressed primarily in beta cells of the pancreatic islets. In Genomics, 82, 130-42. doi:. https://pubmed.ncbi.nlm.nih.gov/12837264/

3. Yesildag, Burcak, Bock, Thomas, Herrmanns, Karolin, Wollscheid, Bernd, Stoffel, Markus. 2015. Kin of IRRE-like Protein 2 Is a Phosphorylated Glycoprotein That Regulates Basal Insulin Secretion. In The Journal of biological chemistry, 290, 25891-906. doi:10.1074/jbc.M115.684704. https://pubmed.ncbi.nlm.nih.gov/26324709/

4. Littman, Meryl P, Wiley, Claire A, Raducha, Michael G, Henthorn, Paula S. 2013. Glomerulopathy and mutations in NPHS1 and KIRREL2 in soft-coated Wheaten Terrier dogs. In Mammalian genome : official journal of the International Mammalian Genome Society, 24, 119-26. doi:10.1007/s00335-012-9445-8. https://pubmed.ncbi.nlm.nih.gov/23325127/

5. Ristola, Mervi, Lehtonen, Sanna. . Functions of the podocyte proteins nephrin and Neph3 and the transcriptional regulation of their genes. In Clinical science (London, England : 1979), 126, 315-28. doi:10.1042/CS20130258. https://pubmed.ncbi.nlm.nih.gov/24219158/