2024
Toxoplasma gondii actin filaments are tuned for rapid disassembly and turnover
Hvorecny K, Sladewski T, De La Cruz E, Kollman J, Heaslip A. Toxoplasma gondii actin filaments are tuned for rapid disassembly and turnover. Nature Communications 2024, 15: 1840. PMID: 38418447, PMCID: PMC10902351, DOI: 10.1038/s41467-024-46111-3.Peer-Reviewed Original ResearchConceptsActin filamentsDynamic properties of actin filamentsProperties of actin filamentsCytoskeletal protein actinFilamentous actin networkSkeletal muscle actinCryo-EM structureIn vitro assemblyOrganelle inheritanceD-loopActin networkNucleotide exchangeLive cell imagingProteins actinSkeletal actinConserved structureEvolutionary changesActinApicomplexan parasitesAssembly contactsIntracellular parasitesMonomer dissociationApicomplexanFilamentsBiophysical properties
2021
Rab34 GTPase mediates ciliary membrane formation in the intracellular ciliogenesis pathway
Ganga AK, Kennedy MC, Oguchi ME, Gray S, Oliver KE, Knight TA, De La Cruz EM, Homma Y, Fukuda M, Breslow DK. Rab34 GTPase mediates ciliary membrane formation in the intracellular ciliogenesis pathway. Current Biology 2021, 31: 2895-2905.e7. PMID: 33989527, PMCID: PMC8282722, DOI: 10.1016/j.cub.2021.04.075.Peer-Reviewed Original ResearchConceptsIntracellular pathwaysCiliary membrane biogenesisCiliary membrane formationIntracellular ciliogenesis pathwayMDCK cellsPolarized MDCK cellsDistinct molecular requirementsPrimary cilia formExtracellular pathwaysTissue-specific mannerCiliary pocketGTPase domainMembrane biogenesisDistinct functional propertiesCiliary vesiclesAssembly intermediatesCilia formSignal transductionGTP bindingMother centriolePrimary ciliaCiliogenesisDivergent residuesIntracellular ciliaRab34Structural basis of fast- and slow-severing actin–cofilactin boundaries
Hocky GM, Sindelar CV, Cao W, Voth GA, De La Cruz EM. Structural basis of fast- and slow-severing actin–cofilactin boundaries. Journal Of Biological Chemistry 2021, 296: 100337. PMID: 33508320, PMCID: PMC7961102, DOI: 10.1016/j.jbc.2021.100337.Peer-Reviewed Original Research
2020
Improving the Pharmacodynamics and In Vivo Activity of ENPP1‐Fc Through Protein and Glycosylation Engineering
Stabach PR, Zimmerman K, Adame A, Kavanagh D, Saeui CT, Agatemor C, Gray S, Cao W, De La Cruz EM, Yarema KJ, Braddock DT. Improving the Pharmacodynamics and In Vivo Activity of ENPP1‐Fc Through Protein and Glycosylation Engineering. Clinical And Translational Science 2020, 14: 362-372. PMID: 33064927, PMCID: PMC7877847, DOI: 10.1111/cts.12887.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArea Under CurveDisease Models, AnimalEnzyme Replacement TherapyGlycosylationHalf-LifeHistocompatibility Antigens Class IHumansMaleMice, TransgenicPhosphoric Diester HydrolasesProtein EngineeringProtein Structure, TertiaryPyrophosphatasesReceptors, FcRecombinant Fusion ProteinsVascular CalcificationConceptsProtein engineeringO-BuN-glycansGlycosylation engineeringCellular recyclingENPP1-deficient miceTerminal sialylationBiomanufacturing platformProtein therapeuticsCalcification disordersSialylationCellsVivo activityFc neonatal receptorTherapeuticsArterial calcificationProteinMurine modelManNAcEnzyme replacementNeonatal receptorEfficacious levelsGeneral strategyThree-prong strategyDrug potencyForce and phosphate release from Arp2/3 complex promote dissociation of actin filament branches
Pandit NG, Cao W, Bibeau J, Johnson-Chavarria EM, Taylor EW, Pollard TD, De La Cruz EM. Force and phosphate release from Arp2/3 complex promote dissociation of actin filament branches. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 13519-13528. PMID: 32461373, PMCID: PMC7306818, DOI: 10.1073/pnas.1911183117.Peer-Reviewed Original ResearchConceptsActin filament branchesArp2/3 complexMother filamentFilament branchesTotal internal reflection fluorescence microscopyEssential cellular functionsMechanical forcesActin filament networkReflection fluorescence microscopyCellular functionsActin networkCell motilityComplex generatesActin filamentsArp2/3Filament networkFluorescence microscopyState 1Branch junctionsState 2FilamentsComplexesPhosphate releaseMuscle actinADPStructures of cofilin-induced structural changes reveal local and asymmetric perturbations of actin filaments
Huehn AR, Bibeau JP, Schramm AC, Cao W, De La Cruz EM, Sindelar CV. Structures of cofilin-induced structural changes reveal local and asymmetric perturbations of actin filaments. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 1478-1484. PMID: 31900364, PMCID: PMC6983403, DOI: 10.1073/pnas.1915987117.Peer-Reviewed Original ResearchConceptsFilament severingActin filamentsSevering activityCofilin/ADF familyActin conformational changesActin filament severingFilament-severing activityCryo-electron microscopy dataSevers actin filamentsWeak severing activityUnique binding modeCofilin clustersActin structuresCofilin bindingCofilin-decorated segmentsCofilinMolecular understandingBarbed endsConformational changesCooperative bindingBinding cooperativityFilament endsPositive cooperativityBinding modesSevering
2019
Regulation of axon growth by myosin II–dependent mechanocatalysis of cofilin activity
Zhang XF, Ajeti V, Tsai N, Fereydooni A, Burns W, Murrell M, De La Cruz EM, Forscher P. Regulation of axon growth by myosin II–dependent mechanocatalysis of cofilin activity. Journal Of Cell Biology 2019, 218: 2329-2349. PMID: 31123185, PMCID: PMC6605792, DOI: 10.1083/jcb.201810054.Peer-Reviewed Original Research
2018
The actin filament twist changes abruptly at boundaries between bare and cofilin-decorated segments
Huehn A, Cao W, Elam WA, Liu X, De La Cruz EM, Sindelar CV. The actin filament twist changes abruptly at boundaries between bare and cofilin-decorated segments. Journal Of Biological Chemistry 2018, 293: 5377-5383. PMID: 29463680, PMCID: PMC5900768, DOI: 10.1074/jbc.ac118.001843.Peer-Reviewed Original ResearchConceptsCofilin-decorated segmentsConformational changesCofilin/ADF proteinsActin-remodeling proteinsBind actin filamentsActin filament interactionsCofilin-induced changesEffects of cofilinCooperative conformational changesProtein occupancyADF proteinsCellular processesCell divisionStructure-based methodsCryo-EMActin segmentsIntracellular transportActin filamentsFilament twistCooperative bindingCofilinTwist changesActinFluorophore labelingSubunits
2016
Architecture and Connectivity Govern Actin Network Contractility
Ennomani H, Letort G, Guérin C, Martiel JL, Cao W, Nédélec F, De La Cruz EM, Théry M, Blanchoin L. Architecture and Connectivity Govern Actin Network Contractility. Current Biology 2016, 26: 616-626. PMID: 26898468, PMCID: PMC4959279, DOI: 10.1016/j.cub.2015.12.069.Peer-Reviewed Original Research
2015
ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy
Albright RA, Stabach P, Cao W, Kavanagh D, Mullen I, Braddock AA, Covo MS, Tehan M, Yang G, Cheng Z, Bouchard K, Yu ZX, Thorn S, Wang X, Folta-Stogniew EJ, Negrete A, Sinusas AJ, Shiloach J, Zubal G, Madri JA, De La Cruz EM, Braddock DT. ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy. Nature Communications 2015, 6: 10006. PMID: 26624227, PMCID: PMC4686714, DOI: 10.1038/ncomms10006.Peer-Reviewed Original ResearchConceptsChronic kidney diseaseVascular calcificationArterial calcificationOrphan diseaseCommon diseaseSequelae of diseaseEctopic vascular calcificationInternal elastic laminaPrevent mortalityRenal failureCardiac failureKidney diseaseSubcutaneous administrationRodent modelsAnimal modelsEctopic calcificationVascular wallLarge arteriesElastic laminaDiseaseCalcificationCalciphylaxisDecreased concentrationSclerosisArteryMetavinculin Tunes the Flexibility and the Architecture of Vinculin-Induced Bundles of Actin Filaments
Durer Z, McGillivary RM, Kang H, Elam WA, Vizcarra CL, Hanein D, De La Cruz EM, Reisler E, Quinlan ME. Metavinculin Tunes the Flexibility and the Architecture of Vinculin-Induced Bundles of Actin Filaments. Journal Of Molecular Biology 2015, 427: 2782-2798. PMID: 26168869, PMCID: PMC4540644, DOI: 10.1016/j.jmb.2015.07.005.Peer-Reviewed Original ResearchConceptsMetavinculin tail domainVinculin tail domainActin filamentsTail domainSevering activityCell-extracellular matrix junctionsF-actinC-terminal tail domainTotal internal reflection fluorescence microscopy experimentsLonger splice isoformsLimited proteolysis experimentsActin filament bundlesFluorescence microscopy experimentsMatrix junctionsSite-directed labelingSplice isoformsAbundant proteinsProteolysis experimentsMuscle cell functionFilament organizationVinculinFilament bundlesInterprotomer contactsCell functionFilament flexibilityActin Mechanics and Fragmentation*
De La Cruz EM, Gardel ML. Actin Mechanics and Fragmentation*. Journal Of Biological Chemistry 2015, 290: 17137-17144. PMID: 25957404, PMCID: PMC4498053, DOI: 10.1074/jbc.r115.636472.Peer-Reviewed Original Research
2013
Regulation of Actin by Ion-Linked Equilibria
Kang H, Bradley MJ, Elam WA, De La Cruz EM. Regulation of Actin by Ion-Linked Equilibria. Biophysical Journal 2013, 105: 2621-2628. PMID: 24359734, PMCID: PMC3882474, DOI: 10.1016/j.bpj.2013.10.032.Peer-Reviewed Original ResearchCompetitive displacement of cofilin can promote actin filament severing
Elam WA, Kang H, De La Cruz EM. Competitive displacement of cofilin can promote actin filament severing. Biochemical And Biophysical Research Communications 2013, 438: 728-731. PMID: 23911787, PMCID: PMC3785092, DOI: 10.1016/j.bbrc.2013.07.109.Peer-Reviewed Original ResearchActin organization and dynamics: novel regulatory mechanisms from the biophysical to the tissue level
Miller AL, De La Cruz EM. Actin organization and dynamics: novel regulatory mechanisms from the biophysical to the tissue level. Molecular Biology Of The Cell 2013, 24: 677-677. PMID: 23486401, PMCID: PMC3596237, DOI: 10.1091/mbc.e12-12-0879.Peer-Reviewed Original ResearchBiophysics of actin filament severing by cofilin
Elam WA, Kang H, De La Cruz EM. Biophysics of actin filament severing by cofilin. FEBS Letters 2013, 587: 1215-1219. PMID: 23395798, PMCID: PMC4079045, DOI: 10.1016/j.febslet.2013.01.062.Peer-Reviewed Original Research
2012
Identification of cation-binding sites on actin that drive polymerization and modulate bending stiffness
Kang H, Bradley MJ, McCullough BR, Pierre A, Grintsevich EE, Reisler E, De La Cruz EM. Identification of cation-binding sites on actin that drive polymerization and modulate bending stiffness. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 16923-16927. PMID: 23027950, PMCID: PMC3479481, DOI: 10.1073/pnas.1211078109.Peer-Reviewed Original ResearchConceptsCation-binding sitesActin assemblyEukaryotic biologyLong-pitch helixActin functionSalt-dependent effectsCell divisionCell motilityActin polymerizationFilament assemblyAdjacent subunitsIntracellular transportActin filamentsPhysiological salt concentrationsActin monomersCellular shapeNonspecific ionic strength effectsDiscrete sitesNPP4 is a procoagulant enzyme on the surface of vascular endothelium
Albright RA, Chang WC, Robert D, Ornstein DL, Cao W, Liu L, Redick ME, Young JI, De La Cruz EM, Braddock DT. NPP4 is a procoagulant enzyme on the surface of vascular endothelium. Blood 2012, 120: 4432-4440. PMID: 22995898, PMCID: PMC4017314, DOI: 10.1182/blood-2012-04-425215.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine DiphosphateAdultAnimalsBlood CoagulationCoagulantsCyclic Nucleotide Phosphodiesterases, Type 4Dinucleoside PhosphatesEndothelium, VascularFluorescent Antibody TechniqueHumansHydrolysisIn Vitro TechniquesInsectaPhosphoric Diester HydrolasesPlatelet AggregationPyrophosphatasesTissue DistributionConceptsPlatelet dense granule componentsNucleotide pyrophosphatase/phosphodiesteraseRelease of ADPUncharacterized enzymesPyrophosphatase/phosphodiesteraseGranule componentsEnzymatic basisRapid disaggregationDense granule releasePlatelet aggregationExtracellular spaceAp3AConcentration-dependent mannerEnzymeGranule releaseVascular endotheliumADPProcoagulant enzymeADP receptorActivationAggregationMutantsActin Network Architecture Can Determine Myosin Motor Activity
Reymann AC, Boujemaa-Paterski R, Martiel JL, Guérin C, Cao W, Chin HF, De La Cruz EM, Théry M, Blanchoin L. Actin Network Architecture Can Determine Myosin Motor Activity. Science 2012, 336: 1310-1314. PMID: 22679097, PMCID: PMC3649007, DOI: 10.1126/science.1221708.Peer-Reviewed Original ResearchATP Utilization and RNA Conformational Rearrangement by DEAD-Box Proteins
Henn A, Bradley MJ, De La Cruz EM. ATP Utilization and RNA Conformational Rearrangement by DEAD-Box Proteins. Annual Review Of Biophysics 2012, 41: 247-267. PMID: 22404686, PMCID: PMC7761782, DOI: 10.1146/annurev-biophys-050511-102243.Peer-Reviewed Original ResearchConceptsDEAD-box proteinsNucleotide-dependent interactionRegulatory partner proteinsMolecular motor proteinsMolecular motor functionPartner proteinsRNA helicasesHelicase coreRNA helicaseRNA metabolismVivo foldingATP bindingDBP functionMotor proteinsCellular RNARNA structureQuantitative mechanistic understandingConformational rearrangementsBiophysical investigationsEnzymatic adaptationLarge familyMechanistic understandingProteinRNAAuxiliary domain