Cathepsin X cleavage of the β2 integrin regulates talin‐binding and LFA‐1 affinity in T cells

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: carboxypeptidase;    activation;    cytoplasmic tail;   

DOI  :  10.1189/jlb.1110622

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Tcellmigration,essentialforimmunesurveillanceandresponse,ismediatedbytheintegrinLFA‐1.CatX,acysteinecarboxypeptidase,isinvolvedintheregulationofTcellmigrationbyinteractionwithLFA‐1.WeshowthatsequentialcleavageofC‐terminalaminoacidsfromtheβ2cytoplasmictailofLFA‐1,byCatX,enhancesbindingoftheadaptorproteintalintoLFA‐1andtriggersformationofthelatterˈshigh‐affinityform.AsshownbySPRanalysisofpeptidesconstitutingthetruncatedβ2tail,thecleavageofthreeC‐terminalaminoacidsbyCatXresultedina1.6‐foldincreaseoftalinbinding.Removalofonemoreaminoacidresultedina2.5‐foldincreaseovertheintacttail.CatXcleavageincreasedtalin‐bindingaffinitytotheMDbutnottheMPtalin‐bindingsiteontheβ2tail.Thiswasshownbymolecularmodelingoftheβ2tail/talinF3complextobearesultofconformationalchangesaffectingprimarilythedistal‐bindingsite.AnalysisofLFA‐1byconformation‐specificmAbshowedthatCatXmodulatesLFA‐1affinity,promotingformationofhigh‐affinityfromintermediate‐affinityLFA‐1butnottheinitialactivationofLFA‐1fromabenttoextendedform.CatXpost‐translationalmodificationsmaythusrepresentamechanismofLFA‐1fine‐tuningthatenablesthetraffickingofTcells...

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