Pathogenic RAB34 variants impair primary cilium assembly and cause a novel oral-facial-digital syndrome
Bruel A, Ganga A, Nosková L, Valenzuela I, Martinovic J, Duffourd Y, Zikánová M, Majer F, Kmoch S, Mohler M, Sun J, Sweeney L, Martínez-Gil N, Thauvin-Robinet C, Breslow D. Pathogenic RAB34 variants impair primary cilium assembly and cause a novel oral-facial-digital syndrome. Human Molecular Genetics 2023, 32: 2822-2831. PMID: 37384395, PMCID: PMC10481091, DOI: 10.1093/hmg/ddad109.Peer-Reviewed Original ResearchConceptsCilia assemblyCiliary membrane formationIntracellular ciliogenesis pathwayPrimary cilia assemblyBi-allelic missense variantsRab proteinsRab GTPaseCiliary proteinsSmall GTPaseNascent ciliaMother centriolePrimary ciliaC-terminusProtein productsPathogenic variantsRab34Cell typesFunctional impactMissense variantsGTPaseStrong lossCiliogenesisSignificant defectsGenesKey mediatorRab34 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 ciliaRab34