PALS1 is essential for retinal pigment epithelium structure and neural retina stratification
| Autor: | B. Park, M. W. Seeliger, Celso H. Alves, Naoyuki Tanimoto, Jan Klooster, Till F. M. Andlauer, A. le Bivic, Eric C. Swindell, Susanne C. Beck, Fabrice Richard, Gesine Huber, Milan Jamrich, Ditte M. S. Lundvig, Jan Wijnholds |
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| Přispěvatelé: | Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Department of Retinal Signal Processing, Netherlands Institute for Neuroscience-KNAW, Réseau National des Systèmes Complexes (RNSC), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CGE-CPU-Centre National de la Recherche Scientifique (CNRS), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Centre National de la Recherche Scientifique (CNRS)-CPU-CGE-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Netherlands Institute for Neuroscience (NIN) |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Genetics and epigenetic pathways of disease [NCMLS 6] genetic structures MESH: Neurons Retinal Pigment Epithelium MESH: Marmota MESH: Mice Knockout Photoreceptor cell chemistry.chemical_compound Mice 0302 clinical medicine MESH: Animals GeneralLiterature_REFERENCE(e.g. dictionaries encyclopedias glossaries) Retinal regeneration Mice Knockout Neurons 0303 health sciences CRB1 medicine.diagnostic_test General Neuroscience MESH: Retina Articles MESH: Retinal Pigment Epithelium Cell biology MESH: Tomography Optical Coherence medicine.anatomical_structure Female MESH: Membrane Proteins Tomography Optical Coherence Mice 129 Strain MESH: Mice Transgenic Outer plexiform layer Mice Transgenic [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Retina 03 medical and health sciences MESH: Mice 129 Strain MESH: Mice Inbred C57BL medicine Animals MESH: Mice 030304 developmental biology Retinal pigment epithelium Membrane Proteins Retinal eye diseases MESH: Male Mice Inbred C57BL Ophthalmoscopy chemistry Marmota MESH: Ophthalmoscopy sense organs Nucleoside-Phosphate Kinase Neuroscience MESH: Female MESH: Nucleoside-Phosphate Kinase 030217 neurology & neurosurgery Electroretinography |
| Zdroj: | Journal of Neuroscience Journal of Neuroscience, Society for Neuroscience, 2011, 31 (47), pp.17230-41. ⟨10.1523/JNEUROSCI.4430-11.2011⟩ Journal of Neuroscience; Vol 31 Journal of Neuroscience, 2011, 31 (47), pp.17230-41. ⟨10.1523/JNEUROSCI.4430-11.2011⟩ The Journal of Neuroscience, 31, 17230-17241 The Journal of Neuroscience, 31, pp. 17230-17241 Journal of Neuroscience, 31, 17230-17241. Society for Neuroscience |
| ISSN: | 0270-6474 1529-2401 |
| Popis: | The membrane-associated palmitoylated protein 5 (MPP5 or PALS1) is thought to organize intracellular PALS1-CRB-MUPP1 protein scaffolds in the retina that are involved in maintenance of photoreceptor–Müller glia cell adhesion. In humans, the Crumbs homolog 1 (CRB1) gene is mutated in progressive types of autosomal recessive retinitis pigmentosa and Leber congenital amaurosis. However, there is no clear genotype–phenotype correlation forCRB1mutations, which suggests that other components of the CRB complex may influence the severity of retinal disease. Therefore, to understand the physiological role of the Crumbs complex proteins, especially PALS1, we generated and analyzed conditional knockdown mice forPals1. Small irregularly shaped spots were detected throughout the PALS1 deficient retina by confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography. The electroretinography a- and b-wave was severely attenuated in the aged mutant retinas, suggesting progressive degeneration of photoreceptors. The histological analysis showed abnormal retinal pigment epithelium structure, ectopic photoreceptor nuclei in the subretinal space, an irregular outer limiting membrane, half rosettes of photoreceptors in the outer plexiform layer, and a thinner photoreceptor synaptic layer suggesting improper photoreceptor cell layering during retinal development. The PALS1 deficient retinas showed reduced levels of Crumbs complex proteins adjacent to adherens junctions, upregulation of glial fibrillary acidic protein indicative of gliosis, and persisting programmed cell death after retinal maturation. The phenotype suggests important functions of PALS1 in the retinal pigment epithelium in addition to the neural retina. |
| Databáze: | OpenAIRE |
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