Ureteric Bud Outgrowth in Response to RET Activation Is Mediated by Phosphatidylinositol 3-Kinase

Developmental Biology

Yang-Kao Wang¹  Ming-Jer Tang¹  Yi Cai¹  Si-Jie Tsai¹  Gregory R. Dressler¹ 

[1] Department of Physiology, National Cheng Kung University Medical College, Tainan, Taiwan

关键词: RET;    GDNF;    phosphatidylinositol 3-kinase;    cell migration;    chemotaxis;   

DOI  :  10.1006/dbio.2001.0557

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

Thec-retgeneencodesareceptortyrosinekinase(RET)essentialforthedevelopmentofthekidneyandentericnervoussystem.ActivationofRETrequiresthesecretedneurotrophinGDNF(glialcellline-derivedneurotrophicfactor)anditshighaffinityreceptor,aglycosylphosphatidylinositol-linkedcellsurfaceproteinGFRα1.Inthedevelopingkidney,RET,GDNF,andGFRα1areallrequiredfordirectedoutgrowthandbranchingmorphogenesisoftheuretericbudepithelium.UsingMDCKrenalepithelialcellsasamodelsystem,activationofRETinducescellmigration,scattering,andformationoffilopodiaandlamellipodia.RET-expressingMDCKcellsareabletomigratetowardalocalizedsourceofGDNF.Inthisreport,theintracellularsignalingmechanismsregulatingRET-dependentmigrationandchemotaxisareexamined.ActivationofRETresultedinincreasedlevelsofphosphatidylinositol3-kinase(PI3K)activityandAkt/PKBphosphorylation.ThisincreaseinPI3KactivityisessentialforregulatingtheGDNFresponse,sincethespecificinhibitor,LY294002,blocksmigrationandchemotaxisofMDCKcells.Usinganinvitroorgancultureassay,inhibitionofPI3KcompletelyblockstheGDNF-dependentoutgrowthofectopicureterbuds.PI3Kisalsoessentialforbranchingmorphogenesisoncetheuretericbudhasinvadedthekidneymesenchyme.ThedatasuggestthatactivationofRETintheuretericbudepitheliumsignalsthroughPI3Ktocontroloutgrowthandbranchingmorphogenesis.

【 授权许可】

Unknown