biostudies-literaturePower KMNIDDK NIH HHSNHGRI NIH HHSNational Institutes of HealthNIH HHSNIGMS NIH HHSNew Jersey Commission on Spinal Cord Researche1009052https://www.ebi.ac.uk/biostudies/studies/S-EPMC7592914biostudies-literatureUnknown16(10)Ciliary microtubules are subject to post-translational modifications that act as a "Tubulin Code" to regulate motor traffic, binding proteins and stability. In humans, loss of CCP1, a cytosolic carboxypeptidase and tubulin deglutamylating enzyme, causes infantile-onset neurodegeneration. In C. elegans, mutations in ccpp-1, the homolog of CCP1, result in progressive degeneration of neuronal cilia and loss of neuronal function. To identify genes that regulate microtubule glutamylation and ciliary integrity, we performed a forward genetic screen for suppressors of ciliary degeneration in ccpp-1 mutants. We isolated the ttll-5(my38) suppressor, a mutation in a tubulin tyrosine ligase-like glutamylase gene. We show that mutation in the ttll-4, ttll-5, or ttll-11 gene suppressed the hyperglutamyPLoS geneticsMutation of NEKL-4/NEK10 and TTLL genes suppress neuronal ciliary degeneration caused by loss of CCPP-1 deglutamylase function.PMC7592914DK116606K12 GM093854CSCR15IRG014R24 OD010943R01 DK116606P40 OD010440U41 HG002223Bellotti SGolden AGu AMorash MZhang WWalsh JDSmith HERoss NO'Hagan RPower KMBarr MMAkella JSRamadan YHfalseMutation of NEKL-4/NEK10 and TTLL genes suppress neuronal ciliary degeneration caused by loss of CCPP-1 deglutamylase function.Ciliary microtubules are subject to post-translational modifications that act as a "Tubulin Code" to regulate motor traffic, binding proteins and stability. In humans, loss of CCP1, a cytosolic carboxypeptidase and tubulin deglutamylating enzyme, causes infantile-onset neurodegeneration. In C. elegans, mutations in ccpp-1, the homolog of CCP1, result in progressive degeneration of neuronal cilia and loss of neuronal function. To identify genes that regulate microtubule glutamylation and ciliary integrity, we performed a forward genetic screen for suppressors of ciliary degeneration in ccpp-1 mutants. We isolated the ttll-5(my38) suppressor, a mutation in a tubulin tyrosine ligase-like glutamylase gene. We show that mutation in the ttll-4, ttll-5, or ttll-11 gene suppressed the hyperglutamy2020-01-01T00:00:00Z2020 Oct2025-06-01T03:53:06.209Z2020-11-08T09:44:40ZS-EPMC75929143306477410.1371/journal.pgen.1009052