| Structural highlights
Function
KIRR3_MOUSE Synaptic adhesion molecule required for the formation of target-specific synapses (PubMed:23637329, PubMed:26575286). Required for formation of target-specific synapses at hippocampal mossy fiber synapses. Required for formation of mossy fiber filopodia, the synaptic structures connecting dentate granule and GABA neurons. Probably acts as a homophilic adhesion molecule that promotes trans-cellular interactions and stabilize mossy fiber filipodia contact and subsequent synapse formation (PubMed:26575286). Required for the coalescence of vomeronasal sensory neuron axons (PubMed:23637329). May be involved in the hematopoietic supportive capacity of stroma cells; the secreted extracellular domain is directly responsible for supporting hematopoietic stem cells (PubMed:12665856).[1] [2] [3]
Publication Abstract from PubMed
Projections from sensory neurons of olfactory systems coalesce into glomeruli in the brain. The Kirrel receptors are believed to homodimerize via their ectodomains and help separate sensory neuron axons into Kirrel2- or Kirrel3-expressing glomeruli. Here, we present the crystal structures of homodimeric Kirrel receptors and show that the closely related Kirrel2 and Kirrel3 have evolved specific sets of polar and hydrophobic interactions, respectively, disallowing heterodimerization while preserving homodimerization, likely resulting in proper segregation and coalescence of Kirrel-expressing axons into glomeruli. We show that the dimerization interface at the N-terminal immunoglobulin (IG) domains is necessary and sufficient to create homodimers and fail to find evidence for a secondary interaction site in Kirrel ectodomains. Furthermore, we show that abolishing dimerization of Kirrel3 in vivo leads to improper formation of glomeruli in the mouse accessory olfactory bulb as observed in Kirrel3(-/-) animals. Our results provide evidence for Kirrel3 homodimerization controlling axonal coalescence.
Molecular and structural basis of olfactory sensory neuron axon coalescence by Kirrel receptors.,Wang J, Vaddadi N, Pak JS, Park Y, Quilez S, Roman CA, Dumontier E, Thornton JW, Cloutier JF, Ozkan E Cell Rep. 2021 Nov 2;37(5):109940. doi: 10.1016/j.celrep.2021.109940. PMID:34731636[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ueno H, Sakita-Ishikawa M, Morikawa Y, Nakano T, Kitamura T, Saito M. A stromal cell-derived membrane protein that supports hematopoietic stem cells. Nat Immunol. 2003 May;4(5):457-63. PMID:12665856 doi:10.1038/ni916
- ↑ Prince JE, Brignall AC, Cutforth T, Shen K, Cloutier JF. Kirrel3 is required for the coalescence of vomeronasal sensory neuron axons into glomeruli and for male-male aggression. Development. 2013 Jun;140(11):2398-408. PMID:23637329 doi:10.1242/dev.087262
- ↑ Martin EA, Muralidhar S, Wang Z, Cervantes DC, Basu R, Taylor MR, Hunter J, Cutforth T, Wilke SA, Ghosh A, Williams ME. The intellectual disability gene Kirrel3 regulates target-specific mossy fiber synapse development in the hippocampus. Elife. 2015 Nov 17;4:e09395. PMID:26575286 doi:10.7554/eLife.09395
- ↑ Wang J, Vaddadi N, Pak JS, Park Y, Quilez S, Roman CA, Dumontier E, Thornton JW, Cloutier JF, Özkan E. Molecular and structural basis of olfactory sensory neuron axon coalescence by Kirrel receptors. Cell Rep. 2021 Nov 2;37(5):109940. PMID:34731636 doi:10.1016/j.celrep.2021.109940
|
