title: The Disease Protein Tulp1 Is Essential for Periactive Zone Endocytosis in Photoreceptor Ribbon Synapses.
abstract: Mutations in the Tulp1 gene cause severe, early-onset retinitis pigmentosa (RP14) in humans. In the retina, Tulp1 is mainly expressed in photoreceptors that use ribbon synapses to communicate with the inner retina. In the present study, we demonstrate that Tulp1 is highly enriched in the periactive zone of photoreceptor presynaptic terminals where Tulp1 colocalizes with major endocytic proteins close to the synaptic ribbon. Analyses of Tulp1 knock-out mice demonstrate that Tulp1 is essential to keep endocytic proteins enriched at the periactive zone and to maintain high levels of endocytic activity close to the synaptic ribbon. Moreover, we have discovered a novel interaction between Tulp1 and the synaptic ribbon protein RIBEYE, which is important to maintain synaptic ribbon integrity. The current findings suggest a new model for Tulp1-mediated localization of the endocytic machinery at the periactive zone of ribbon synapses and offer a new rationale and mechanism for vision loss associated with genetic defects in Tulp1.
authors.affiliation: Institute for Anatomy and Cell Biology, Department of Neuroanatomy, Saarland University, Medical School Homburg/Saar, 66421 Homburg/Saar, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Wahl
authors.affiliation: Institute for Anatomy and Cell Biology, Department of Neuroanatomy, Saarland University, Medical School Homburg/Saar, 66421 Homburg/Saar, Germany.
authors.forename: Venkat Giri
authors.initials: VG
authors.lastname: Magupalli
authors.affiliation: Institute for Anatomy and Cell Biology, Department of Neuroanatomy, Saarland University, Medical School Homburg/Saar, 66421 Homburg/Saar, Germany.
authors.forename: Mayur
authors.initials: M
authors.lastname: Dembla
authors.affiliation: Institute for Anatomy and Cell Biology, Department of Neuroanatomy, Saarland University, Medical School Homburg/Saar, 66421 Homburg/Saar, Germany.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Katiyar
authors.affiliation: Institute for Anatomy and Cell Biology, Department of Neuroanatomy, Saarland University, Medical School Homburg/Saar, 66421 Homburg/Saar, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Schwarz
authors.affiliation: Institute for Anatomy and Cell Biology, Department of Neuroanatomy, Saarland University, Medical School Homburg/Saar, 66421 Homburg/Saar, Germany.
authors.forename: Louise
authors.identifier: http://orcid.org/0000-0003-2139-0573
authors.initials: L
authors.lastname: Köblitz
authors.affiliation: Institute for Anatomy and Cell Biology, Department of Neuroanatomy, Saarland University, Medical School Homburg/Saar, 66421 Homburg/Saar, Germany.
authors.forename: Kannan
authors.initials: K
authors.lastname: Alpadi
authors.affiliation: Institute of Physiology, Saarland University, Medical School Homburg/Saar, 66421 Homburg/Saar, Germany.
authors.forename: Elmar
authors.initials: E
authors.lastname: Krause
authors.affiliation: Institute of Physiology, Saarland University, Medical School Homburg/Saar, 66421 Homburg/Saar, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Rettig
authors.affiliation: Margaret M. Dyson Vision Research Institute, Department of Ophthalmology, Cell and Developmental Biology, Weill Medical College of Cornell University, New York, New York 10021, and.
authors.forename: Ching-Hwa
authors.initials: CH
authors.lastname: Sung
authors.affiliation: Eye Research Institute, Oakland University, Rochester, Michigan 48309.
authors.forename: Andrew F X
authors.identifier: http://orcid.org/0000-0002-3964-5987
authors.initials: AF
authors.lastname: Goldberg
authors.affiliation: Institute for Anatomy and Cell Biology, Department of Neuroanatomy, Saarland University, Medical School Homburg/Saar, 66421 Homburg/Saar, Germany, frank.schmitz@uks.eu.
authors.forename: Frank
authors.identifier: http://orcid.org/0000-0003-1457-6222
authors.initials: F
authors.lastname: Schmitz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D004705:Endocytosis / Q000502:physiology*; D005136:Eye Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009924:Organ Culture Techniques; D010786:Photoreceptor Cells / Q000737:chemistry / Q000378:metabolism*; D012160:Retina / Q000737:chemistry / Q000378:metabolism; D013569:Synapses / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D005136:Eye Proteins; C491353:Tulp1 protein, mouse
keywords: RIBEYE; Tulp1; endocytosis; periactive zone; photoreceptor synapse; ribbon synapse