2024
Modulation of FGF pathway signaling and vascular differentiation using designed oligomeric assemblies.
Edman NI, Phal A, Redler RL, Schlichthaerle T, Srivatsan SR, Ehnes DD, Etemadi A, An SJ, Favor A, Li Z, Praetorius F, Gordon M, Vincent T, Marchiano S, Blakely L, Lin C, Yang W, Coventry B, Hicks DR, Cao L, Bethel N, Heine P, Murray A, Gerben S, Carter L, Miranda M, Negahdari B, Lee S, Trapnell C, Zheng Y, Murry CE, Schweppe DK, Freedman BS, Stewart L, Ekiert DC, Schlessinger J, Shendure J, Bhabha G, Ruohola-Baker H, Baker D. Modulation of FGF pathway signaling and vascular differentiation using designed oligomeric assemblies. Cell 2024, 187: 3726-3740.e43. PMID: 38861993, DOI: 10.1016/j.cell.2024.05.025.Peer-Reviewed Original Research
2023
Heparin is essential for optimal cell signaling by FGF21 and for regulation of βKlotho cellular stability
An S, Mohanty J, Tome F, Suzuki Y, Lax I, Schlessinger J. Heparin is essential for optimal cell signaling by FGF21 and for regulation of βKlotho cellular stability. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2219128120. PMID: 36745784, PMCID: PMC9962926, DOI: 10.1073/pnas.2219128120.Peer-Reviewed Original ResearchConceptsHeparan sulfate proteoglycanCellular stabilityCell membraneSingle-molecule fluorescenceProtein kinase responsesChinese hamster ovary cellsFGF moleculesHamster ovary cellsFactor bindsReceptor assemblyReceptor dimerizationGrowth factor bindsHigh-affinity bindingFGF1 stimulationKinase responseCHO cellsOvary cellsSulfate proteoglycanIntracellular CaKlotho proteinFGFR1cPotential roleRegulationΒKlothoCells
2022
Regulation of EGF-stimulated activation of the PI-3K/AKT pathway by exocyst-mediated exocytosis
An S, Anneken A, Xi Z, Choi C, Schlessinger J, Toomre D. Regulation of EGF-stimulated activation of the PI-3K/AKT pathway by exocyst-mediated exocytosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2208947119. PMID: 36417441, PMCID: PMC9860279, DOI: 10.1073/pnas.2208947119.Peer-Reviewed Original ResearchConceptsPI-3K/Akt pathwayAkt pathwayAkt activationDocking protein Gab1EGF-stimulated activationEpithelial cellsLive-cell imagingPhosphoinositide-3 kinaseCell survival pathwaysExocyst complexExocyst functionSmall molecule inhibitorsVesicle tethersExocytic fusionProtein Gab1EGF stimulationExocystSurvival pathwaysExocytosisInhibitors resultsPathwayImportant pathwayEGFR inhibitionMinute time scaleVesiclesMultimodal imaging of synaptic vesicles with a single probe
An SJ, Stagi M, Gould TJ, Wu Y, Mlodzianoski M, Rivera-Molina F, Toomre D, Strittmatter SM, De Camilli P, Bewersdorf J, Zenisek D. Multimodal imaging of synaptic vesicles with a single probe. Cell Reports Methods 2022, 2: 100199. PMID: 35497490, PMCID: PMC9046237, DOI: 10.1016/j.crmeth.2022.100199.Peer-Reviewed Original ResearchConceptsC2 domainSynaptic vesiclesSynaptic vesicle recyclingMembrane-binding C2 domainMultiple microscopy methodsEndocytic markersMembrane recyclingVesicle functionVesicle populationsCytosolic phospholipase ACell typesPhospholipase ADetectable tagMicroscopy modalitiesModular probesMultiple microscopy techniquesVesiclesComplete understandingDomainMicroscopy methodsMultiple levelsProbeAvailable probesMicroscopy techniquesPathway
2021
An active tethering mechanism controls the fate of vesicles
An SJ, Rivera-Molina F, Anneken A, Xi Z, McNellis B, Polejaev VI, Toomre D. An active tethering mechanism controls the fate of vesicles. Nature Communications 2021, 12: 5434. PMID: 34521845, PMCID: PMC8440521, DOI: 10.1038/s41467-021-25465-y.Peer-Reviewed Original ResearchConceptsArtificial tetherFull fusionOptogenetic controlExocyst complexExocyst functionVesicle tethersMembrane mergerTethering mechanismTarget membraneIntracellular fusionPlasma membraneMode of fusionVesicle fusionPhysiological relevanceLamellipodial expansionVesiclesTetheringExocystMembraneFusionFurther showTetherFusion modeFateComplexes
2020
FGF23 contains two distinct high-affinity binding sites enabling bivalent interactions with α-Klotho
Suzuki Y, Kuzina E, An SJ, Tome F, Mohanty J, Li W, Lee S, Liu Y, Lax I, Schlessinger J. FGF23 contains two distinct high-affinity binding sites enabling bivalent interactions with α-Klotho. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 31800-31807. PMID: 33257569, PMCID: PMC7749347, DOI: 10.1073/pnas.2018554117.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesCalcinosisCell MembraneFibroblast Growth Factor-23Fibroblast Growth FactorsGlucuronidaseHEK293 CellsHumansHyperostosis, Cortical, CongenitalHyperphosphatemiaImmunoglobulin Fc FragmentsKlotho ProteinsMutationOsteomalaciaProtein BindingProtein DomainsProtein MultimerizationRecombinant Fusion ProteinsRickets, HypophosphatemicConceptsFGF receptorsTotal internal reflection fluorescence microscopyChimeric receptor moleculesReflection fluorescence microscopyBinding sitesDisulfide bridge formationCritical metabolic processesMAPK responseCytoplasmic domainGrowth factor familyTerminal tailFactor familyKinase activationSimilar binding affinitiesExtracellular domainFGFR1 activationTandem repeatsMetabolic processesDisulfide bridgesCell surfaceDistinct ligandsCell membraneFluorescence microscopyDistinct high-affinity binding sitesPhosphate homeostasis