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P Dubreuil

Publications and source records attributed to P Dubreuil.

At least 19 recordsLinked to original sources
PubMed2007

Effect of protein supply on hepatic synthesis of plasma and constitutive proteins in lactating dairy cows.

The effects of metabolizable protein (MP) supply on the synthesis of plasma total proteins and albumin, as well as total hepatic protein synthesis, were determined in 6 multicatheterized lactating Holstein cows. Three TMR formulated to supply the same amount of energy but different amounts of MP, 1,922 (low), 2,264 (medium), and 2,517 g of MP/d (high), were fed every 2 h according to a double 3 x 3 Latin square design. For the low and high MP treatments, the cows were continuously infused with [(2)H(5)]Phe (d5-Phe) into a jugular vein for 8 h (1.3 mmol/h) on d 21 of each period. Concentration and isotopic enrichment of d5-Phe were measured for free plasma Phe, plasma total proteins, and albumin on hourly samples collected between 3 and 8 h. Low MP decreased the plasma albumin concentration (32.3 vs. 33.7 +/- 0.11 g/L) but the plasma total protein concentration was unchanged (74.1 vs. 75.6 +/- 1.13 g/L). Incorporation of d5-Phe over time into both plasma total proteins and albumin was linear (R(2) > 0.98). Neither fractional nor absolute synthesis rates of plasma total proteins (6.8 vs. 6.5 +/- 0.65%/d; 168 vs. 154 +/- 19.9 g/d) or albumin (3.4 vs. 3.4 +/- 0.10%/d; 36.3 vs. 36.5 +/- 1.11 g/d) were affected by the MP supply. Net hepatic removal of Phe was lower with the low-MP diet (-12.3 vs. -20.2 +/- 1.98 mmol/h). As a result, net hepatic Phe removal used for total export protein synthesis (17.9 vs. 11.1 +/- 1.83%) and albumin synthesis (4.6 vs. 2.9 +/- 0.54%) tended to be greater at low MP. These results suggest that hepatic synthesis of plasma proteins, including albumin, is maintained in lactating dairy cows even when the protein supply is reduced.

Animal Nutritional Physiological Phenomena↗
PubMed2006

Semaxinib (SU5416) as a therapeutic agent targeting oncogenic Kit mutants resistant to imatinib mesylate.

Activating mutations in the Kit receptor are frequently observed in various malignancies, pointing Kit as a molecule of interest for drug inhibition. When mutated on Asp 816 (corresponding to Asp 814 in the mouse), as preferentially found in human mastocytosis and acute myeloid leukemia, Kit became non-sensitive to imatinib mesylate (Gleevec). Erythroleukemic cells isolated from Spi-1/PU.1 transgenic mice express Kit mutated at codon 814 (Kit(D814Y) or Kit(D814V)) or codon 818 (Kit(D818Y)). Using these cells in vitro, we demonstrate that the tyrosine kinase inhibitor SU5416 (Semaxinib) induces growth arrest and apoptosis independent of the mutation type by inhibiting the functions of Kit, including Kit autophosphorylation and activation of Akt, Erk1/Erk2 and Stat3 downstream signaling pathways. These findings indicate that SU5416 may be a promising tool to kill cancer cells driven by Kit oncogenic mutations that are resistant to treatment with imatinib mesylate.

Animals↗
PubMed2006

Field study of the efficacy of halofuginone and decoquinate in the treatment of cryptosporidiosis in veal calves.

Ninety, seven- to 10-day-old calves were allocated to three groups of 30 and treated daily for seven days with either 100 microg/kg halofuginone hydrobromide or 2.5 mg/kg decoquinate orally or left untreated as controls. The levels of diarrhoea and dehydration were monitored daily for 28 days from the first day of treatment (day 0) and samples of faeces were collected on days 0, 7, 14, 21 and 28, to quantify the excretion of Cryptosporidium parvum oocysts. The calves were weighed on days 3 and 28. The treatments had no effect on the levels of diarrhoea or dehydration, the proportions of diarrhoeic calves or the proportions of calves shedding oocysts. However, unlike decoquinate, halofuginone significantly reduced the excretion of oocysts on day 7 (P<0.0001), and decoquinate increased the average daily weight gain of the calves (P=0.049).

Animals↗
PubMed2006

[Optimisation of retrospective diagnosis of cytomegalovirus congenital infection from dried blood spots].

Out of the 90% of cytomegalovirus (CMV) congenitally infected children that are asymptomatic at birth, 5 to 15% will later develop complications, mainly neurodevelopmental defects and/or deafness. Unfortunately, after the first 2 weeks of life, usual diagnostic techniques for CMV detection (viral culture and serology) are useless to differentiate congenital infection from post-natal acquired infection, whereas detection of viral DNA from dried blood spots (DBS; Guthrie cards), systematically collected from all newborns in the first days of life, has been described for late diagnosis of CMV congenital infection. The aim of our study was to choose and optimise a viral DNA extraction method from DBS and to study if CMV DNA detection is reliable when DBS are stored for 1 year at room temperature or 2 months at 37 degrees C. 10 reference cards (blood collected from CMV seronegative newborns (IgG/IgM negative) were "infected" with serial dilutions of virus and spotted on Guthrie cards) were tested. 3 extraction methods were evaluated, products of PCR were analyzes by agarose gel electrophoresis and quantification of CMV from DBS was also performed. Analysis of the results obtained from reference cards showed higher sensitivity of phenol/chloroform extraction following treatment with proteinase K, compared to heat extraction in cell culture medium or extraction with a commercial kit. We did not observe quantitative loss of viral DNA after 1 year storage at room temperature. CMV DNA detection from Guthrie cards could become a very useful tool for retrospective diagnosis of congenital CMV infection when sequelae are diagnosed in the first years of life. We are pursuing this study with DBS from congenitally infected children.

Cytomegalovirus↗
PubMed2006

Correlated break at PARK2/FRA6E and loss of AF-6/Afadin protein expression are associated with poor outcome in breast cancer.

Common fragile sites (CFSs) are regions of chromosomal break that may play a role in oncogenesis. The most frequent alteration occurs at FRA3B, within the FHIT gene, at chromosomal region 3p14. We studied a series of breast carcinomas for break of a CFS at 6q26, FRA6E, and its associated gene PARK2, using fluorescence in situ hybridization on tissue microarrays (TMA). We found break of PARK2 in 6% of cases. We studied the PARK2-encoded protein Parkin by using immunohistochemistry on the same TMA. Loss of Parkin was found in 13% of samples but was not correlated with PARK2 break. PARK2 break but not Parkin expression was correlated with prognosis. Alteration of PARK2/FRA6E may cause haplo-insufficiency of one or several telomeric potential tumor suppressor genes (TSG). The AF-6/MLLT4 gene, telomeric of PARK2, encodes the Afadin scaffold protein, which is essential for epithelial integrity. Loss of Afadin was found in 14.5% of cases, and 36% of these cases showed PARK2 break. Loss of Afadin had prognostic impact, suggesting that AF-6 may be a TSG. Loss of Afadin was correlated with loss of FHIT expression, suggesting fragility of FRA6E and FRA3B in a certain proportion of breast tumors.

Acid Anhydride Hydrolases↗
PubMed2006

Effect of ruminally protected methionine on splanchnic metabolism of amino acids in lactating dairy cows.

The effect of ruminally protected Met (RPM) on splanchnic metabolism was measured in 3 primiparous and 3 multiparous Holstein cows. Doses of RPM (0, 36, and 72 g/d) were tested in a replicated 3 x 3 Latin square design, over 3 consecutive 14-d experimental periods. A mixed ration was fed in 12 equal meals per d (average dry matter intake: 17.5 +/- 0.08 kg/d). Indwelling catheters were surgically implanted in the mesenteric artery and the portal and hepatic veins for blood collection, as well as in 2 distal branches of the mesenteric vein for infusion of p-aminohippurate to determine blood flow. On d 14 of each period, a temporary catheter was inserted into a mammary vein and 6 hourly blood samples were collected to determine plasma concentrations of metabolites, hormones, and their respective fluxes across the splanchnic bed and mammary glands. Yields of milk (32.8, 32.0, and 32.9 +/- 0.92 kg/d) and protein (1,028, 1,053, and 1,075 +/- 28.7 g/d) were unaffected by level of RPM. However, the true protein content in milk from primiparous cows increased linearly (2.92, 3.09, and 3.34 +/- 0.077%). The addition of RPM linearly increased the net flux of Met across the portal-drained viscera, which resulted in increased arterial Met concentrations (25, 29, and 40 +/- 1.1 microM). Although it had no significant effect on net portal and hepatic fluxes of other essential amino acids, RPM resulted in a linear increase in the total splanchnic output of Ile, Leu, Phe, and Thr. These results suggest that feeding RPM triggered a homeostatic response resulting in less utilization of certain essential amino acids through the gastrointestinal tract and liver. Net mammary uptake of Met did not change with the addition of RPM. However, mammary extraction of Met decreased in a linear fashion in response to increased arterial inflow.

Amino Acids↗
PubMed2006

What is the true supply of amino acids for a dairy cow?

Improving the prediction of milk protein yield relies on knowledge of both protein supply and requirement. Definition of protein/amino acid supply in ruminants is a challenging task, due to feedstuff variety and variability and to the remodeling of nutrient intake by the rumen microflora. The questions arise, therefore, how and where should we measure the real supply of AA in the dairy cow? This review will follow the downstream flow of AA from duodenum to peripheral tissue delivery, with a glance at the efficiency of transfer into milk protein. Duodenal AA flow comprises rumen undegradable feed, microbial protein, and endogenous secretions. Most attention has been directed toward definition of the first two contributions but the latter fraction can represent as much as 20% of duodenal flow. More information is needed on what factors affect its magnitude and overall impact. Once digested, AA are absorbed into the portal vein. The ratio of portal absorption to small intestinal apparent digestion varies among essential AA, from 0.43 (threonine) to 0.76 (phenylalanine), due to the contributions of preduodenal endogenous secretions to the digestive flow, non-reabsorption of endogenous secretions and gut oxidation of AA. Few data are available on these phenomena in dairy cows but the evidence indicates that they alter the profile of AA available for anabolic purposes. Recent comparisons of estimated duodenal flux and measured portal flux have prompted a revisit of the NRC (2001) approach to estimate AA flows at the duodenum. Changes to the model are proposed that yield predictions that better fit the current knowledge of AA metabolism across the gut. After absorption, AA flow first to the liver where substantial and differential net removal occurs, varying from zero for the branched-chain AA to 50% of portal absorption for phenylalanine. This process alters the pattern of net supply to the mammary gland. Overall, intermediary metabolism of AA between the duodenum and the mammary gland biologically explains the decreased efficiency of the transfer of absorbed AA into milk protein as maximal yield is approached. Therefore, variable, rather than fixed, factors for transfer efficiencies must be incorporated into future predictive models.

Absorption↗
PubMed2006

Effect of postruminal glutamine supplementation on immune response and milk production in dairy cows.

Seventeen multiparous Holstein cows were used to examine the effect of an increased duodenal supply of Gln on immune function and production. Cows received continuous abomasal infusions of water (control: n = 8) or 300 g/d of Gln (n = 9) for 21 d starting within 48 h of calving. There were nonsignificant increases in milk and milk protein yields in response to Gln supplementation. Glutamine treatment had no effect on plasma glucose, nonesterified fatty acids (NEFA), or beta-hydroxybutyrate (BHBA) concentrations but did tend to increase plasma urea N concentration. The Gln treatment resulted in an increase of 108 microM in the plasma Gln concentration. Total essential AA concentrations decreased with the Gln treatment, whereas total nonessential AA concentrations were unaffected. T Lymphocyte proliferation did not differ between the control and Gln-treated cows. Treatment had no effect on the relative abundance of CD8 T cells but did increase the abundance of CD4 T cells. Cytokine production, as measured by IFN-gamma concentration determined in vitro in concanavalin-A-stimulated peripheral blood mononuclear cells, was similar between the treatments. Over the first 3 wk following calving, Gln supplementation had limited effects on milk production, metabolic parameters, and immune function.

3-Hydroxybutyric Acid↗
PubMed2005

Microsatellite marker polymorphism and mapping in pea (Pisum sativum L.).

This paper aims at providing reliable and cost effective genotyping conditions, level of polymorphism in a range of genotypes and map position of newly developed microsatellite markers in order to promote broad application of these markers as a common set for genetic studies in pea. Optimal PCR conditions were determined for 340 microsatellite markers based on amplification in eight genotypes. Levels of polymorphism were determined for 309 of these markers. Compared to data obtained for other species, levels of polymorphism detected in a panel of eight genotypes were high with a mean number of 3.8 alleles per polymorphic locus and an average PIC value of 0.62, indicating that pea represents a rather polymorphic autogamous species. One of our main objectives was to locate a maximum number of microsatellite markers on the pea genetic map. Data obtained from three different crosses were used to build a composite genetic map of 1,430 cM (Haldane) comprising 239 microsatellite markers. These include 216 anonymous SSRs developed from enriched genomic libraries and 13 SSRs located in genes. The markers are quite evenly distributed throughout the seven linkage groups of the map, with 85% of intervals between the adjacent SSR markers being smaller than 10 cM. There was a good conservation of marker order and linkage group assignment across the three populations. In conclusion, we hope this report will promote wide application of these markers and will allow information obtained by different laboratories worldwide in diverse fields of pea genetics, such as QTL mapping studies and genetic resource surveys, to be easily aligned.

Chromosome Mapping↗
PubMed2005

Biochemical reference ranges for groups of ewes of different ages.

Reference biochemical ranges for young adult and adult ewes in mid-gestation were derived from 83 pooled serum samples taken from 30 flocks in the Province of Québec, Canada. In each flock the samples were pooled into three age categories and each category contained between six and 10 samples. The blood samples were taken by jugular venepuncture in December 1999. All the values were within the normal published ranges. As the age of the ewes increased there were slight increases in the concentrations of globulin and total protein and decreases in the concentrations of calcium, phosphorus, creatinine, glucose and albumin, and in the activities of alkaline phosphatase and glutathione peroxidase.

Aging↗
PubMed2004

Effect of level of metabolizable protein on splanchnic flux of amino acids in lactating dairy cows.

The response of splanchnic tissue metabolism to different levels of metabolizable protein (MP) was measured in 6 catheterized multiparous lactating Holstein cows. Three diets, balanced to provide similar energy intakes and increasing amounts of MP (g/d)-1922 (low), 2264 (medium), and 2517 (high)-were fed during 21-d experimental periods according to a replicated Latin square. On d 18, 19, or 20, six hourly blood samples were collected simultaneously from the portal and hepatic veins plus an artery to determine net fluxes of nutrients across the portal-drained viscera and the liver. Yields of milk and protein increased, as did urinary N excretion with increasing MP. Portal absorption of essential amino acids (EAA) increased linearly with increasing MP supply, as did liver removal of His, Met, and Phe. In contrast, liver removal of the branched-chain AA (BCAA) and lysine was unaffected by diets. With increasing MP, the ratio of milk output to postliver supply of BCAA, Thr, and Lys decreased linearly, indicating oxidation of these AA in the peripheral tissues. Concomitant to a decreased catabolism of EAA in the liver (His, Met, Phe, and Thr) and/or in peripheral tissues (BCAA, Lys, and Thr), the efficiency of transfer of absorbed EAA into milk protein decreases markedly as protein supply increases. The efficiency of transfer of absorbed AA into milk also varies greatly between AA. These 2 important factors should be taken into account when building predictive schemes for milk protein output.

Amino Acids↗
PubMed2003

Functional characterization of human CD34+ cells that express low or high levels of the membrane antigen CD111 (nectin 1).

Nectins are recently described adhesion molecules that are widely expressed on many tissues, including the hematopoietic tissue. Nectin 1 (CD111) is expressed on a higher proportion of mobilized peripheral blood (mPB) than cord blood (CB) CD34+ cells, and of CD34+/CD38+ cells when compared with CD34+/CD38- cells. We studied functional properties of human CB and mPB CD34+ cells that express low or high levels of CD111. CD34+/CD111(dim) cells contain a higher proportion of cells in G0/G1 phase than CD34+/CD111(bright) cells. CD34+/CD111(bright) cells contain more erythroid progenitors: CFU-E, than their counterparts, which on the opposite contain more HPP-CFC. Limiting dilution analyses demonstrate a higher frequency of immature progenitors: cobblestone-area colony-forming cells, CD34+/CD111(dim) than in CD34+/CD111(bright) cells. In vitro differentiation assays demonstrate a higher frequency of B-, T- and dendritic-cell precursors, but less NK-cell precursors in CD34+/CD111(dim) cells. Evaluation of engraftment in NOD-SCID mice shows that SCID repopulating cells are more frequent among mPB CD34+/CD111(dim) cells. Liquid culture of CD34+/CD111(dim) cells with erythropoietin shows that CD111 expression increases simultaneously with CD36, following CD71 and before glycophorin A expression. In conclusion, immature human hematopoietic progenitors express low levels of CD111 on their surface. During erythroid differentiation CD34+ cells acquire higher levels of the CD111 antigen.

Animals↗
PubMed2002

Maize introduction into Europe: the history reviewed in the light of molecular data.

The resolution that can be obtained from molecular genetic markers affords new prospects for understanding the dispersion of agricultural species from their primary origin centres. In order to study the introduction and the dispersion of maize in Europe, we have characterised a large and representative set of maize populations of both American and European origins for their variation at 29 restriction fragment length polymorphism loci. Polymorphism was higher for American populations than for European populations (respectively, 12.3 and 9.6 alleles per locus, on average), and only a few alleles were specific to European populations. Investigation of genetic similarity between populations from both continents made it possible to identify various types of American maize introduced into Europe at different times or in different places and which have given rise to distinctive European races. Beyond confirming the importance of Caribbean germplasm, the first maize type to be introduced into Europe, this research revealed that introductions of Northern American flint populations have played a key role in the adaptation of maize to the European climate. According to a detailed historical investigation, the introduction of these populations must have occurred shortly after the discovery of the New World.

Europe↗
PubMed2002

Effect of supply of metabolizable protein on splanchnic fluxes of nutrients and hormones in lactating dairy cows.

The effect of the supply of metabolizable protein on splanchnic fluxes of nutrients and hormones was measured in six catheterized late-lactation Holstein cows in a crossover design. Two isonitrogenous diets (16.3% CP), but differing in rumen protein degradability and estimated metabolizable protein (MP) supply (1654 g/ d, Lo-MP; 1930 g/d, Hi-MP) were fed, each over a 35-d experimental period. On d 34 or 35, net fluxes of nutrients and hormones across the portal-drained viscera, the liver, and total splanchnic tissues were determined. Portal absorption of total, essential, nonessential, and branched-chain amino acids (AA) increased with the Hi-MP diet. Approximately 76% of the additional metabolizable protein supply was recovered as extra AA-N absorption in the portal vein. Liver removal of AA was not different between diets, and this resulted in a greater net release across the splanchnic tissues for the Hi-MP diet. This extra AA supply provided substrates for the observed increased milk protein yield for the Hi-MP diet. Fractional efficiencies of conversion of absorbed individual essential AA into milk protein ranged from 0.42 to 0.68. The corresponding efficiencies for utilization of postsplanchnic AA supply were 0.42 to 1.80. Provision of methionine, phenylalanine, and histidine beyond the liver were similar to outputs in milk protein but the other essential AA were supplied to peripheral tissues in excess of milk output, indicative of oxidative mechanisms in nonhepatic tissues. Net fluxes of glucose, NH3-N, and urea were not affected by the diets. Neither arterial concentrations of insulin, somatotropin, or IGF-1, nor net transfers across the portal-drained viscera or liver of insulin, were affected by the diets. Although portal release of glucagon was not different between the diets, a smaller proportion was removed by the liver on the Hi-MP diet. Metabolism of AA across the splanchnic tissue bed is a major determinant of the quantity and the profile of AA delivered to peripheral tissues.

Amino Acids↗
PubMed2002

Effect of supply of metabolizable protein on whole body and splanchnic leucine metabolism in lactating dairy cows.

The effect of the supply of metabolizable protein (MP) on protein metabolism across the splanchnic tissues was determined in six catheterized lactating Holstein cows. In a crossover design, two isonitrogenous (16.3% CP) diets balanced to provide a low (Lo-MP) or high (Hi-MP) supply of MP were fed over 35-d periods. After 24 d of feeding, N balance was determined over a 6-d period. On d 33, [13C] sodium bicarbonate was infused into one jugular vein for 6 h, and hourly breath samples were collected. On d 34 or 35, L[1-(13)C] leucine was infused into one jugular vein, and between 2 to 6 h of infusion, breath and blood samples were taken hourly from the portal and hepatic veins and an artery. Isotopic enrichments of plasma leucine, 4-methyl-2-oxopentanoate, and expired CO2 were determined for calculation of leucine kinetics. Net leucine absorption was greater, either on a direct basis (leucine transfer only) or corrected for portal-drained viscera metabolism to 4-methyl-2-oxopentanoate and CO2 for the Hi-MP diet. There were no effects of diet on hepatic net flux of leucine across the liver, and, thus, more leucine was available to peripheral tissues with the Hi-MP diet. Combined with an increment in portal absorption of most of essential AA, this led to increased milk protein output, although it only represented 16% of the additional available leucine. Whole body leucine oxidation was also greater for the Hi-MP diet, as was leucine used for protein synthesis. Despite these changes, MP supply did not affect irreversible loss rate of leucine by portal-drained viscera and the liver; these averaged 35 and 20% of whole body irreversible loss rate, respectively. These ratios confirm the high metabolic activity of splanchnic tissues in lactating dairy cows, which are even greater than previously reported in growing ruminants.

Animal Nutritional Physiological Phenomena↗
PubMed2001

Kit signaling and negative regulation of daunorubicin-induced apoptosis: role of phospholipase Cgamma.

Previous studies have demonstrated that activation of Kit by stem cell factor (SCF), its natural ligand, or by gain-of-function point mutation in its intracellular domain, confers significant protection against apoptosis induced by growth factor deprivation or radiation. However, the effects of Kit activation on the cellular response to anti-tumor agents have not been so extensively documented. This study shows that daunorubicin-induced apoptosis and cytotoxicity were reduced in the murine Ba/F3 cells transfected with Kit (Ba/F3-Kit) in the presence of SCF and in Ba/F3 cells transfected with a constitutively active Kit variant (Ba/F3-KitDelta27), compared to either parental Ba/F3 (Ba/F3-wt) or unstimulated Ba/F3-Kit cells. In Ba/F3-wt and in Ba/F3-Kit cells, daunorubicin stimulated within 8-15 min neutral sphingomyelinase and ceramide production but not in SCF-stimulated Ba/F3-Kit or in Ba/F3-KitDelta27 whereas all Ba/F3 cells were equally sensitive to exogenous cell-permeant C6-ceramide. In Ba/F3-Kit, SCF-induced Kit activation resulted in a rapid phospholipase Cgamma (PLCgamma) tyrosine phosphorylation followed by diacylglycerol release and protein kinase C (PKC) stimulation. U-73122, a PLCgamma inhibitor, not only blocked diacylglycerol production and PKC stimulation but also restored daunorubicin-induced sphingomyelinase stimulation, ceramide production, and apoptosis. These results suggest that Kit activation results in PLCgamma-mediated PKC-dependent sphingomyelinase inhibition which contributes to drug resistance in Kit-related malignancies.

Animals↗
PubMed2001

Nectin4/PRR4, a new afadin-associated member of the nectin family that trans-interacts with nectin1/PRR1 through V domain interaction.

Nectins are adhesion molecules that participate in the organization of epithelial and endothelial junctions and serve as receptors for herpes simplex virus entry. They belong to the immunoglobulin superfamily, are homologues of the poliovirus receptor (PVR/CD155), and were also named poliovirus receptor-related (PRR) proteins. We identify a new member of the nectin family named nectin4. Peptide sequences of human and murine nectin4 share 92% identity, and as for other members, the ectodomain is made of three immunoglobulin-like domains of V, C, C types. In contrast to other nectin molecules, detection of nectin4 transcripts is mainly restricted to placenta in human tissues. Expression is broader in mouse, and interestingly nectin4 is detected at days 11, 15, and 17 during murine embryogenesis. Nectin4 interacts with afadin, a F-actin-associated molecule, via its carboxyl-terminal cytoplasmic sequence. Both molecules co-localize at cadherin-based adherens junctions in the MDCKII epithelial cell line. Nectins are homophilic adhesion molecules, and recently heterophilic interactions have been described between nectin3/nectin1 and nectin3/nectin2. We confirmed these trans-interactions and also described nectin3 as the PVR/CD155 ligand. By means of several approaches, we report on the identification of nectin4 as a new ligand for nectin1. First, a soluble chimeric recombinant nectin4 ectodomain (nectin4-Fc) trans-interacts with cells expressing nectin1 but not with cells expressing nectin2, nectin3, or PVR/CD155. Conversely, nectin1-Fc binds to cells expressing nectin4. Second, nectin1-Fc precipitates nectin4 expressed in COS cells. Third, reciprocal in vitro physical interactions were detected between nectin4-Fc and nectin1-Fc. The nectin4-Fc/nectin4-Fc interaction was detected suggesting that nectin4 exhibits both homophilic and heterophilic properties. Using the same approaches we demonstrate, for the first time, that the V domain of nectin1 acts as a major functional region involved in trans-heterointeraction with nectin4 and also nectin3.

Actins↗