title: Alterations in the balance of tubulin glycylation and glutamylation in photoreceptors leads to retinal degeneration.
abstract: Tubulin is subject to a wide variety of posttranslational modifications, which, as part of the tubulin code, are involved in the regulation of microtubule functions. Glycylation has so far predominantly been found in motile cilia and flagella, and absence of this modification leads to ciliary disassembly. Here, we demonstrate that the correct functioning of connecting cilia of photoreceptors, which are non-motile sensory cilia, is also dependent on glycylation. In contrast to many other tissues, only one glycylase, TTLL3, is expressed in retina.Ttll3-/-mice lack glycylation in photoreceptors, which results in shortening of connecting cilia and slow retinal degeneration. Moreover, absence of glycylation results in increased levels of tubulin glutamylation in photoreceptors, and inversely, the hyperglutamylation observed in the Purkinje cell degeneration (pcd) mouse abolishes glycylation. This suggests that both posttranslational modifications compete for modification sites, and that unbalancing the glutamylation-glycylation equilibrium on axonemes of connecting cilia, regardless of the enzymatic mechanism, invariably leads to retinal degeneration.
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3348, Orsay F-91405, France.|Université Paris Sud, Université Paris-Saclay, CNRS UMR3348, Orsay F-91405, France.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Bosch Grau
authors.affiliation: CERTO Centre d'Etudes et de Recherches Thérapeutiques en Ophtalmologie, Université Paris Sud, Université Paris-Saclay, CNRS UMR9197, Orsay F-91405, France.
authors.forename: Christel
authors.initials: C
authors.lastname: Masson
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3348, Orsay F-91405, France.|Université Paris Sud, Université Paris-Saclay, CNRS UMR3348, Orsay F-91405, France.
authors.forename: Sudarshan
authors.initials: S
authors.lastname: Gadadhar
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3348, Orsay F-91405, France.|Université Paris Sud, Université Paris-Saclay, CNRS UMR3348, Orsay F-91405, France.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Rocha
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3348, Orsay F-91405, France.|Université Paris Sud, Université Paris-Saclay, CNRS UMR3348, Orsay F-91405, France.
authors.forename: Olivia
authors.initials: O
authors.lastname: Tort
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3348, Orsay F-91405, France.|Université Paris Sud, Université Paris-Saclay, CNRS UMR3348, Orsay F-91405, France.
authors.forename: Patricia
authors.identifier: 0000-0002-6045-4077
authors.initials: P
authors.lastname: Marques Sousa
authors.affiliation: Institut Curie, PSL Research University, Department of Genetics, Paris F-75005, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Vacher
authors.affiliation: Institut Curie, PSL Research University, Department of Genetics, Paris F-75005, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris F-75005, France.
authors.forename: Ivan
authors.initials: I
authors.lastname: Bieche
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3348, Orsay F-91405, France Carsten.Janke@curie.fr.|Université Paris Sud, Université Paris-Saclay, CNRS UMR3348, Orsay F-91405, France.
authors.forename: Carsten
authors.identifier: 0000-0001-7053-2000
authors.initials: C
authors.lastname: Janke
mesh_terms: D000818:Animals; D017209:Apoptosis; D002923:Cilia / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006031:Glycosylation; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D010453:Peptide Synthases / Q000378:metabolism; D010641:Phenotype; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism* / Q000473:pathology*; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000378:metabolism* / Q000473:pathology*; D012243:Rhodopsin / Q000378:metabolism; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism*
chemical_list: D014404:Tubulin; D018698:Glutamic Acid; D012243:Rhodopsin; D010453:Peptide Synthases
keywords: Connecting cilia; Glutamylation; Glycylation; Microtubule; Photoreceptor; Retina; TTLL3; Tubulin