Intracellular Cell-Autonomous Association of Notch and Its Ligands: A Novel Mechanism of Notch Signal Modification

Developmental Biology

Osamu Ohara¹  Kei Sakamoto¹  Minoru Takagi¹  Ken-ichi Katsube¹  Shin'ichi Takeda¹ 

[1] Department of Oral Restitution, Division of Oral Health Sciences, Graduate School, Tokyo Medical & Dental University, Bunkyo-ku, Tokyo, 113-8549, Japan

关键词: cell-autonomous;    association;    Notch;    Delta;    Serrate;   

DOI  :  10.1006/dbio.2001.0517

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

Notch(N)anditsligands,Delta(Dl)andSerrate(Ser),aremembrane-spanningproteinswithEGFrepeats.Theyplayanessentialroleinmediatingproliferationandsegregateddifferentiationofstemcells.OneoftheprominentfeaturesofNsignalsystemisthatitsligandsareanchoredtotheplasmamembrane,whichallowstheligand/receptorassociationonlybetweentheneighboringcells.Variouslinesofevidenceshaveverifiedthisintercellularsignaltransmission,buttherealsohavebeenimplicationsthatexpressionofDlorSerinterferescell-autonomouslywiththeabilityofthecelltoreceiveNsignal,implyingthatNanditsligandsmayinteractinthesamecell.Here,wedemonstratethatN,Dl,andSercell-autonomouslyformhomomericorheteromericcomplexes.Thecell-autonomousheteromericcomplexesarenotpresentonthecellsurface,implyingthattheassociationoccursintheendoreticulumorGolgiapparatus.ExpressionofDlorSercell-autonomouslyreducestheN-mediatedHES-5promoteractivity,indicatingthatthecell-autonomousassociationalterstheNsignalreceptivity.IntracellulardeletionofDlshowselevatedactivityofthisdominant-negativeeffect.Invivooverexpressionstudysuggeststhatthecell-autonomousfunctionofDlandSerisindependentoftheligandspecificityandmaybemodulatedbyFringe(Fg),whichinhibitstheformationofthecell-autonomousDl/NorSer/Ncomplex.

【 授权许可】

Unknown