nectin-3

Nectin-3 has three splicing variants, nectin-3α, which is the biggest one, nectin-3β and the smallest variant nectin-3γ.

Nectin-3α (same as the other splicing variants) is abundately expressed in testis, on slightly lower level it is also expressed in heart, brain, liver or kidney. It has been also proved that nectin-3α is together with nectin-2 localize at the junctional complex regions in small intestina absorptive epithelia. Nectin-3γ is also detectable in lung, liver and kidney. Nectin-3 is expressed not only on epithelial cells as another nectins, but there was shown that, as the only member of nectin family, it is expressed also on T- lymphocytes.{{cite journal | vauthors = Devilard E, Xerri L, Dubreuil P, Lopez M, Reymond N | title = Nectin-3 (CD113) interacts with Nectin-2 (CD112) to promote lymphocyte transendothelial migration | journal = PLOS ONE | volume = 8 | issue = 10 | pages = e77424 | date = 2013-10-07 | pmid = 24116228 | pmc = 3792040 | doi = 10.1371/journal.pone.0077424 | bibcode = 2013PLoSO...877424D | doi-access = free }}

The structural properties of nectin-3α is similar to nectin-1, it has three Ig-like domains at the extracellular region and the C-terminal conserved motif at the cytoplasmic region. The homology of aa (amino aci)) of extracellular domains between Nectin-1 and Nectin-3α is 35,9%. Another splicing variants vary in the number of aa, molecular weight and the structural properties. All of them have the identical extracellular region. Nectin-3β and nectin-3γ have the same transmembrane and cytoplasmic regions, which vary from nectin-3α. Nectin-3γ lack of C-terminal domain. With the intracellular domain nectins bind their assosicated adaptor protein afadin{{cite journal | vauthors = Miyoshi J, Takai Y | title = Nectin and nectin-like molecules: biology and pathology | journal = American Journal of Nephrology | volume = 27 | issue = 6 | pages = 590–604 | date = 2007 | pmid = 17823505 | doi = 10.1159/000108103 | s2cid = 42662486 | doi-access = free }} which plays role in the formation of variety of cell-cell junctions.{{cite journal | vauthors = Takai Y, Ikeda W, Ogita H, Rikitake Y | title = The immunoglobulin-like cell adhesion molecule nectin and its associated protein afadin | journal = Annual Review of Cell and Developmental Biology | volume = 24 | issue = 1 | pages = 309–342 | date = 2008-11-01 | pmid = 18593353 | doi = 10.1146/annurev.cellbio.24.110707.175339 }} Nectin-3γ in not able to bind afadin due to lacking C-terminal domain.

All nectins are able to form cis-homo dimer interactions, which simply means they can create dimer of two alike molecules on the same cell membrane. Further, nectin-3α can also interact with Nectin-1/2α in so called trans-hetero interaction.

Most of the publications deal with nectin-3 regardless the splicing variants, thus this page follows this concept.

Nectin-3 is expressed by granule cells in dentate gyrus and the expression levels are developmentally regulated and reduced by early postnatal stress. On mice model, it has been shown that the early-life stress impaires the long-term spatial memory and temporal order memory. It is also very probable that the nectin-3 in dentate gyrus neurons modulate adult neurogenesis and dendritic spine plasticity.{{cite journal | vauthors = Wang XX, Li JT, Xie XM, Gu Y, Si TM, Schmidt MV, Wang XD | title = Nectin-3 modulates the structural plasticity of dentate granule cells and long-term memory | journal = Translational Psychiatry | volume = 7 | issue = 9 | pages = e1228 | date = September 2017 | pmid = 28872640 | doi = 10.1038/tp.2017.196 | pmc = 5639241 }} It has been proven that combination nectin-3/nectin-1 is very important in formation of synapses in brain, hippocampus and that the formation of hetero-trans-dimers between nectin-1 and nectin-3 determines the position and size of the synapses, in vitro.{{cite journal | vauthors = Mizoguchi A, Nakanishi H, Kimura K, Matsubara K, Ozaki-Kuroda K, Katata T, Honda T, Kiyohara Y, Heo K, Higashi M, Tsutsumi T, Sonoda S, Ide C, Takai Y | display-authors = 6 | title = Nectin: an adhesion molecule involved in formation of synapses | journal = The Journal of Cell Biology | volume = 156 | issue = 3 | pages = 555–565 | date = February 2002 | pmid = 11827984 | pmc = 2173327 | doi = 10.1083/jcb.200103113 }} In vivo, it has been shown that the function of nectin-3 is crutial during the critical periods of the visual cortex development and that it is important not only for synapses formation but also for the synaptic refinement. Also it has been proven that there is a high importance of nectin-3 for the dendritic spine densities (which simply represent the sites of synaptic contacts) on visual cortical neurons.{{Cite journal | vauthors = Tomorsky J, Parker PR, Doe CQ, Niell CM | journal = bioRxiv |date=2019-12-10|title=Precise levels of Nectin-3 and an interaction with Afadin are required for proper synapse formation in postnatal visual cortex| doi = 10.1101/870691 | s2cid = 219723291 | doi-access = free}} The nectin-1/nectin-3 trans-interaction has been shown to be very important to establishing the adhesion between the pigment and non-pigment cell layers of the ciliary epithelia, which is essential for the morphogenesis of the ciliary body of the eye.{{cite journal | vauthors = Inagaki M, Irie K, Ishizaki H, Tanaka-Okamoto M, Morimoto K, Inoue E, Ohtsuka T, Miyoshi J, Takai Y | display-authors = 6 | title = Roles of cell-adhesion molecules nectin 1 and nectin 3 in ciliary body development | journal = Development | volume = 132 | issue = 7 | pages = 1525–1537 | date = April 2005 | pmid = 15728677 | doi = 10.1242/dev.01697 | s2cid = 24560202 | doi-access = free }}

Nectin-3 is important role player in spermatid development. The nectin-3^–/– male mice were found to have defects in the later steps of sperm morphogenesis, exhibiting distorted nuclei and abnormal distribution of mitochondria. The loss of nectin-3 in male mice leads to male-specific infertility.{{cite journal | vauthors = Inagaki M, Irie K, Ishizaki H, Tanaka-Okamoto M, Miyoshi J, Takai Y | title = Role of cell adhesion molecule nectin-3 in spermatid development | journal = Genes to Cells | volume = 11 | issue = 9 | pages = 1125–1132 | date = September 2006 | pmid = 16923130 | doi = 10.1111/j.1365-2443.2006.01006.x | s2cid = 39799813 | doi-access = free }} It has been shown that the chronic stress negatively influences the amnout of nectin-3 in the testis and also the male spermatogenesis function.{{cite journal | vauthors = Li T, Yao J, Zhang Q, Li Q, Li J, Wang X, Li W, Chen A, Yan J | display-authors = 6 | title = Chronic stress impairs male spermatogenesis function and Nectin-3 protein expression in the testis | journal = Physiological Research | volume = 69 | issue = 2 | pages = 297–306 | date = April 2020 | pmid = 32324042 | doi = 10.33549/physiolres.934287 | pmc = 8565941 }}

As mentioned above, nectin-3 is the only nectin which is expressed on T- lymphocytes. The interaction between nectin-3 on T-cells and other nectins on epithelial cells is very important in the lymphocyte transendothelial migration, in vitro. It has been shown that this process is dependent on nectin-2, which is expressed on epithelial cells, the blockation of nectin-2 or nectin-3 leads to inhibition of lymphocyte and also monocyte extravasation.{{cite journal | vauthors = Devilard E, Xerri L, Dubreuil P, Lopez M, Reymond N | title = Nectin-3 (CD113) interacts with Nectin-2 (CD112) to promote lymphocyte transendothelial migration | journal = PLOS ONE | volume = 8 | issue = 10 | pages = e77424 | date = 2013-10-07 | pmid = 24116228 | doi = 10.1371/journal.pone.0077424 | pmc = 3792040 | bibcode = 2013PLoSO...877424D | doi-access = free }}

Nectin-3 is highly expressed in epithelial cancer cells of human lung adenocarcinoma. It is expressed in 80% of patients which makes it relatively strong prognostic marker. It has been shown, there are various expression patterns of nectin-3; cytoplasmic, membranous or combined. The membranous expression is connected with significantly poorer prognosis, patients with this type of expression pattern are also more likely to earlier relapse and death.{{cite journal | vauthors = Maniwa Y, Nishio W, Okita Y, Yoshimura M | title = Expression of nectin 3: Novel prognostic marker of lung adenocarcinoma | journal = Thoracic Cancer | volume = 3 | issue = 2 | pages = 175–181 | date = May 2012 | pmid = 28920296 | doi = 10.1111/j.1759-7714.2011.00104.x | s2cid = 6861003 | doi-access = free }} Increased amounts of nectin-3 are also detectable in ovaries during the ovarian cancer and are correlated with poor patient prognosis. The data also suggest that the possible mechanism of nectin-3 in cellular invasion and migration is by upregulating the expression of matrix metalloproteinases (MMPs) MMP2 and MMP9 in ovarian cancer.{{cite journal | vauthors = Xu F, Si X, Wang J, Yang A, Qin T, Yang Y | title = Nectin-3 is a new biomarker that mediates the upregulation of MMP2 and MMP9 in ovarian cancer cells | journal = Biomedicine & Pharmacotherapy | volume = 110 | pages = 139–144 | date = February 2019 | pmid = 30469078 | doi = 10.1016/j.biopha.2018.11.020 | s2cid = 53764287 | doi-access = free }}

Contrary to previously mentioned cancers, the amount of nectin-3 negatively correlates with Pancreatic neuroendocrine tumors. The loss of this protein correlates with increased tumor progressiveness.{{cite journal | vauthors = Hirabayashi K, Tajiri T, Bosch DE, Morimachi M, Miyaoka M, Inomoto C, Nakamura N, Yeh MM | display-authors = 6 | title = Loss of nectin-3 expression as a marker of tumor aggressiveness in pancreatic neuroendocrine tumor | journal = Pathology International | volume = 70 | issue = 2 | pages = 84–91 | date = February 2020 | pmid = 31855317 | doi = 10.1111/pin.12881 | s2cid = 209418057 }}

Nectin-3 has been shown to interact with:

• MLLT4,{{cite journal | vauthors = Reymond N, Borg JP, Lecocq E, Adelaide J, Campadelli-Fiume G, Dubreuil P, Lopez M | title = Human nectin3/PRR3: a novel member of the PVR/PRR/nectin family that interacts with afadin | journal = Gene | volume = 255 | issue = 2 | pages = 347–355 | date = September 2000 | pmid = 11024295 | doi = 10.1016/s0378-1119(00)00316-4 }}
• PARD3,{{cite journal | vauthors = Takekuni K, Ikeda W, Fujito T, Morimoto K, Takeuchi M, Monden M, Takai Y | title = Direct binding of cell polarity protein PAR-3 to cell-cell adhesion molecule nectin at neuroepithelial cells of developing mouse | journal = The Journal of Biological Chemistry | volume = 278 | issue = 8 | pages = 5497–5500 | date = February 2003 | pmid = 12515806 | doi = 10.1074/jbc.C200707200 | doi-access = free }}
• PTPRM.{{cite journal | vauthors = Sakamoto Y, Ogita H, Komura H, Takai Y | title = Involvement of nectin in inactivation of integrin alpha(v)beta(3) after the establishment of cell-cell adhesion | journal = The Journal of Biological Chemistry | volume = 283 | issue = 1 | pages = 496–505 | date = January 2008 | pmid = 17965016 | doi = 10.1074/jbc.M704195200 | doi-access = free }}

{{Reflist}}

{{Cell adhesion molecules}}

{{Clusters of differentiation}}

Category:Cell adhesion molecules

Category:Clusters of differentiation