2024
Ataxin-2 polyglutamine expansions aberrantly sequester TDP-43 ribonucleoprotein condensates disrupting mRNA transport and local translation in neurons
Wijegunawardana D, Nayak A, Vishal S, Venkatesh N, Gopal P. Ataxin-2 polyglutamine expansions aberrantly sequester TDP-43 ribonucleoprotein condensates disrupting mRNA transport and local translation in neurons. Developmental Cell 2024 PMID: 39419034, DOI: 10.1016/j.devcel.2024.09.023.Peer-Reviewed Original ResearchRNA-binding proteinsAtaxin-2PolyQ expansionTDP-43Like-SmLocal translationAmyotrophic lateral sclerosisDNA-binding proteinsTransactive response DNA-binding proteinLocalization of mRNAAssociated with increased riskRNA metabolismCytoskeletal mRNAsMRNA transportPolyglutamine expansionRNP condensatesMotor neuron axonsRegulatory functionsRibonucleoproteinMotor neuron integrityNeuronal integrityCortical neuronsLiquid-like propertiesNeuronal axonsMotility
2023
Phase separation and pathologic transitions of RNP condensates in neurons: implications for amyotrophic lateral sclerosis, frontotemporal dementia and other neurodegenerative disorders
Naskar A, Nayak A, Salaikumaran M, Vishal S, Gopal P. Phase separation and pathologic transitions of RNP condensates in neurons: implications for amyotrophic lateral sclerosis, frontotemporal dementia and other neurodegenerative disorders. Frontiers In Molecular Neuroscience 2023, 16: 1242925. PMID: 37720552, PMCID: PMC10502346, DOI: 10.3389/fnmol.2023.1242925.Peer-Reviewed Original ResearchAberrant phase transitionsMRNA transportFormation of ribonucleoproteinMembrane-less organellesPathogenic protein aggregationStress granule assemblyALS/frontotemporal dementiaSynaptic functionNeurodegenerative diseasesProcessing bodiesCajal bodiesRNA processingHigher-order structureSpatiotemporal regulationStress granulesTransport granulesAmyotrophic lateral sclerosisGranule assemblyProtein aggregationBiomolecular condensatesMRNA stabilityGene expressionLocal translationPhysiological functionsRBPs
2022
Sequence Determinants of TDP-43 Ribonucleoprotein Condensate Formation and Axonal Transport in Neurons
Vishal SS, Wijegunawardana D, Salaikumaran MR, Gopal PP. Sequence Determinants of TDP-43 Ribonucleoprotein Condensate Formation and Axonal Transport in Neurons. Frontiers In Cell And Developmental Biology 2022, 10: 876893. PMID: 35646935, PMCID: PMC9133736, DOI: 10.3389/fcell.2022.876893.Peer-Reviewed Original ResearchAmyotrophic lateral sclerosisTDP-43A315TAxonal transportTDP-43 variantsMotor neuron degenerationTDP-43 mutationsNeuron degenerationLateral sclerosisTransport deficitsAnterograde transportNeuronsK mutationDisease-linked mutationsMotilityKey determinantPossible mechanismMutationsPrevious findingsRetrograde motilityTransport granulesAdaptor proteinSclerosisDeterminantsGranule transport
2019
Expression of WIPI2B counteracts age-related decline in autophagosome biogenesis in neurons
Stavoe A, Gopal P, Gubas A, Tooze S, Holzbaur E. Expression of WIPI2B counteracts age-related decline in autophagosome biogenesis in neurons. ELife 2019, 8: e44219. PMID: 31309927, PMCID: PMC6634969, DOI: 10.7554/elife.44219.Peer-Reviewed Original ResearchConceptsAmyotrophic lateral sclerosisAged miceNovel therapeutic targetLate-onset neurodegenerative diseasesAge-associated neurodegenerationAge-related declineAged neuronsRisk factorsLateral sclerosisParkinson's diseaseTherapeutic targetLC3B-positive autophagosomesNeurodegenerative diseasesMammalian neuronsNeuronsSignificant decreaseDiseaseRate of autophagy
2017
Amyotrophic lateral sclerosis-linked mutations increase the viscosity of liquid-like TDP-43 RNP granules in neurons
Gopal PP, Nirschl JJ, Klinman E, Holzbaur EL. Amyotrophic lateral sclerosis-linked mutations increase the viscosity of liquid-like TDP-43 RNP granules in neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e2466-e2475. PMID: 28265061, PMCID: PMC5373408, DOI: 10.1073/pnas.1614462114.Peer-Reviewed Original ResearchConceptsRNA-binding proteinRNP granulesAmyotrophic lateral sclerosis-linked mutationsCritical cellular processesRapid fluorescence recoveryAmyotrophic lateral sclerosisBiophysical propertiesDistinct biophysical propertiesRibonucleoprotein granulesSubcellular contextCellular processesSpecific RNAToxic gainTAR-DNA binding protein 43Superresolution microscopyFluorescence recoveryLiquid-liquid phase separationMutant TDP-43Primary cortical neuronsLiquid-like propertiesTDP-43RNAProteinMutationsAxonal location