Overexpression of guanylate cyclase activating protein 2 in rod photoreceptors in vivo leads to morphological changes at the synaptic ribbon

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Title: Overexpression of guanylate cyclase activating protein 2 in rod photoreceptors in vivo leads to morphological changes at the synaptic ribbon
Authors: López del Hoyo, Natalia | Fazioli, Lucrezia | López Begines, Santiago | Fernández-Sánchez, Laura | Cuenca, Nicolás | Llorens Baucells, Jordi | Villa Polo, Pedro de la | Méndez Zunzunegui, Ana
Research Group/s: Neurobiología del Sistema Visual y Terapia de Enfermedades Neurodegenerativas (NEUROVIS)
Center, Department or Service: Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología
Keywords: Retinal degeneration
Knowledge Area: Biología Celular
Issue Date: 13-Aug-2012
Publisher: Public Library of Science (PLoS)
Citation: LÓPEZ-DEL HOYO, Natalia, et al. “Overexpression of guanylate cyclase activating protein 2 in rod photoreceptors in vivo leads to morphological changes at the synaptic ribbon”. PLoS ONE 7(8): e42994. doi:10.1371/journal.pone.0042994
Abstract: Guanylate cyclase activating proteins are EF-hand containing proteins that confer calcium sensitivity to retinal guanylate cyclase at the outer segment discs of photoreceptor cells. By making the rate of cGMP synthesis dependent on the free intracellular calcium levels set by illumination, GCAPs play a fundamental role in the recovery of the light response and light adaptation. The main isoforms GCAP1 and GCAP2 also localize to the synaptic terminal, where their function is not known. Based on the reported interaction of GCAP2 with Ribeye, the major component of synaptic ribbons, it was proposed that GCAP2 could mediate the synaptic ribbon dynamic changes that happen in response to light. We here present a thorough ultrastructural analysis of rod synaptic terminals in loss-of-function (GCAP1/GCAP2 double knockout) and gain-of-function (transgenic overexpression) mouse models of GCAP2. Rod synaptic ribbons in GCAPs−/− mice did not differ from wildtype ribbons when mice were raised in constant darkness, indicating that GCAPs are not required for ribbon early assembly or maturation. Transgenic overexpression of GCAP2 in rods led to a shortening of synaptic ribbons, and to a higher than normal percentage of club-shaped and spherical ribbon morphologies. Restoration of GCAP2 expression in the GCAPs−/− background (GCAP2 expression in the absence of endogenous GCAP1) had the striking result of shortening ribbon length to a much higher degree than overexpression of GCAP2 in the wildtype background, as well as reducing the thickness of the outer plexiform layer without affecting the number of rod photoreceptor cells. These results indicate that preservation of the GCAP1 to GCAP2 relative levels is relevant for maintaining the integrity of the synaptic terminal. Our demonstration of GCAP2 immunolocalization at synaptic ribbons at the ultrastructural level would support a role of GCAPs at mediating the effect of light on morphological remodeling changes of synaptic ribbons.
Sponsor: This work was supported by grants from the Spanish Ministry of Science and Innovation to A.M. (BFU2008-04199/BFI and BFU2011-26519/BFI), to J.Ll. (BFU2009-06945), to P.dlV. (SAF2010-21879 and RETICS RD07/0062/0008), to N.C. (BFU2009-07793/BFI and RETICS RD07/0062/0012); from the European Community to A.M. (Marie-Curie Reintegration grant 210042/RODCELL) and from The Bellvitge Biomedical Research Institute (IDIBELL) to A.M. (10IDB012). N.L.-H. was the recipient of an Bellvitge Biomedical Research Institute (IDIBELL) PhD fellowship.
URI: http://hdl.handle.net/10045/25017
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0042994
Language: eng
Type: info:eu-repo/semantics/article
Rights: © López-del Hoyo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Peer Review: si
Publisher version: http://dx.doi.org/10.1371/journal.pone.0042994
Appears in Collections:INV - NEUROVIS - Artículos de Revistas

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