An Antibody to the Lutheran Glycoprotein (Lu) Recognizing the LU4 Blood Type Variant Inhibits Cell Adhesion to Laminin α5 英文参考文献.docVIP
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An Antibody to the Lutheran Glycoprotein (Lu) Recognizing the LU4 Blood Type Variant Inhibits Cell Adhesion to Laminin α5 英文参考文献
AnAntibodytotheLutheranGlycoprotein(Lu)
RecognizingtheLU4BloodTypeVariantInhibitsCell
AdhesiontoLaminina5
YamatoKikkawa*,TakahiroMiwa,YukikoTohara,TakayukiHamakubo,MotoyoshiNomizu
LaboratoryofClinicalBiochemistry,TokyoUniversityofPharmacyandLifeSciences,Tokyo,Japan
Abstract
Background:TheLutheranbloodgroupglycoprotein(Lu),anIgsuperfamily(IgSF)transmembranereceptor,isalsoknown
asbasalcelladhesionmolecule(B-CAM).Lu/B-CAMisaspecificreceptorforlaminina5,amajorcomponentofbasement
membranesinvarioustissues.PreviousreportshaveshownthatLu/B-CAMbindingtolaminina5contributestosicklecell
vaso-occlusion. However, as there are no useful tools such as function-blocking antibodies or drugs, it is unclear how
epithelialandsickledredbloodcellsadheretolaminina5viaLu/B-CAM.
Methodology/Principal Findings: In this study, we discovered a function-blocking antibody that inhibits Lu binding to
laminina5usingauniquebindingassayontissuesections.Tocharacterizethefunction-blockingantibody,weidentified
thesiteonLu/B-CAMrecognizedbythisantibody.TheextracellulardomainofLu/B-CAMcontainsfiveIgSFdomains,D1-D2-
D3-D4-D5.TheantibodyepitopewaslocalizedtoD2,butnottotheD3domaincontainingthemajorpartofthelaminina5
binding site. Furthermore, mutagenesis studies showed that Arg175, the LU4 blood group antigenic site, was crucial for
formingtheepitopeandtheantibodyboundsufficientlyclosetostericallyhindertheinteractionwith a5.Celladhesion
assayusingtheantibodyalsoshowedthatLu/B-CAMservesasasecondaryreceptorfortheadhesionofcarcinomacellsto
laminina5.
Conclusion/Significance:Thisfunction-blockingantibodyagainstLu/B-CAMshouldbeusefulfornotonlyinvestigatingcell
adhesiontolaminina5butalsofordevelopingdrugstoinhibitsicklecellvaso-occlusion.
Citation:KikkawaY,MiwaT,ToharaY,HamakuboT,NomizuM(2011)AnAntibodytotheLutheranGlycoprotein(Lu)RecognizingtheLU4BloodTypeVariant
InhibitsCellAdhesiontoLaminina5.PLoSONE6(8):e23329.doi:10.1371/journal.pone.0023329
Editor:IvanCruzMoura,InstitutNationaldelaSante′ etde
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