Endoplasmic reticulum exit sites are segregated for secretion based on cargo size
Saxena S, Foresti O, Liu A, Androulaki S, Pena Rodriguez M, Raote I, Aridor M, Cui B, Malhotra V. Endoplasmic reticulum exit sites are segregated for secretion based on cargo size. Developmental Cell 2024, 59: 2593-2608.e6. PMID: 38991587, DOI: 10.1016/j.devcel.2024.06.009.Peer-Reviewed Original ResearchEndoplasmic reticulum exit sitesProline-rich domainC-terminal proline-rich domainCOPII assemblyExit siteER membraneCargo exportJuxtanuclear regionU2OS cellsCargo moleculesBulky cargoSEC23AOptimal secretionCollagen VIIHuman osteosarcomaProlonged bindingComplex organismsCargoCargo sizeBindingCollagen ICTAGE5TANGO1COPIIERGIC53TANGO1 inhibitors reduce collagen secretion and limit tissue scarring
Raote I, Rosendahl A, Häkkinen H, Vibe C, Küçükaylak I, Sawant M, Keufgens L, Frommelt P, Halwas K, Broadbent K, Cunquero M, Castro G, Villemeur M, Nüchel J, Bornikoel A, Dam B, Zirmire R, Kiran R, Carolis C, Andilla J, Loza-Alvarez P, Ruprecht V, Jamora C, Campelo F, Krüger M, Hammerschmidt M, Eckes B, Neundorf I, Krieg T, Malhotra V. TANGO1 inhibitors reduce collagen secretion and limit tissue scarring. Nature Communications 2024, 15: 3302. PMID: 38658535, PMCID: PMC11043333, DOI: 10.1038/s41467-024-47004-1.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulum exit sitesECM proteinsSecretion of ECM proteinsPeptide inhibitorFibrotic diseasesCollagen exportTANGO1Binding interfaceWound healingZebrafish resultsECM componentsReduced granulation tissue formationGranulation tissue formationEffective therapyCutaneous wound healingInhibitor treatmentFibrotic processUncontrolled secretionWidespread occurrenceProtein levelsExit siteExcessive scarringAmount of collagenTherapeutic modulationTissue scarring