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Eur J Neurosci. 2015 Aug;42(3):1966-75. doi: 10.1111/ejn.12959. Epub 2015 Jul 4.

LRIT3 is essential to localize TRPM1 to the dendritic tips of depolarizing bipolar cells and may play a role in cone synapse formation.

Neuillé M1,2,3, Morgans CW4, Cao Y5, Orhan E1,2,3, Michiels C1,2,3, Sahel JA1,2,3,6,7,8,9, Audo I1,2,3,6,7, Duvoisin RM4, Martemyanov KA5, Zeitz C1,2,3.

Author information

1
INSERM, U968, Paris, F-75012, France.
2
CNRS, UMR_7210, Paris, F-75012, France.
3
Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, F-75012, France.
4
Department of Physiology & Pharmacology, Oregon Health & Science University, Portland, OR, 97239, USA.
5
Department of Neuroscience, The Scripps Research Institute, Jupiter, FL, 33458, USA.
6
Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, DHU ViewMaintain, INSERM-DHOS CIC, 1423, Paris, F-75012, France.
7
Institute of Ophthalmology, University College of London, London, EC1V 9EL, UK.
8
Fondation Ophtalmologique Adolphe de Rothschild, Paris, F-75019, France.
9
Académie des Sciences-Institut de France, Paris, F-75006, France.

Abstract

Mutations in LRIT3 lead to complete congenital stationary night blindness (cCSNB). The exact role of LRIT3 in ON-bipolar cell signaling cascade remains to be elucidated. Recently, we have characterized a novel mouse model lacking Lrit3 [no b-wave 6, (Lrit3(nob6/nob6) )], which displays similar abnormalities to patients with cCSNB with LRIT3 mutations. Here we compare the localization of components of the ON-bipolar cell signaling cascade in wild-type and Lrit3(nob6/nob6) retinal sections by immunofluorescence confocal microscopy. An anti-LRIT3 antibody was generated. Immunofluorescent staining of LRIT3 in wild-type mice revealed a specific punctate labeling in the outer plexiform layer (OPL), which was absent in Lrit3(nob6/nob6) mice. LRIT3 did not co-localize with ribeye or calbindin but co-localized with mGluR6. TRPM1 staining was severely decreased at the dendritic tips of all depolarizing bipolar cells in Lrit3(nob6/nob6) mice. mGluR6, GPR179, RGS7, RGS11 and Gβ5 immunofluorescence was absent at the dendritic tips of cone ON-bipolar cells in Lrit3(nob6/nob6) mice, while it was present at the dendritic tips of rod bipolar cells. Furthermore, peanut agglutinin (PNA) labeling was severely reduced in the OPL in Lrit3(nob6/nob6) mice. This study confirmed the localization of LRIT3 at the dendritic tips of depolarizing bipolar cells in mouse retina and demonstrated the dependence of TRPM1 localization on the presence of LRIT3. As tested components of the ON-bipolar cell signaling cascade and PNA revealed disrupted localization, an additional function of LRIT3 in cone synapse formation is suggested. These results point to a possibly different regulation of the mGluR6 signaling cascade between rod and cone ON-bipolar cells.

KEYWORDS:

complete CSNB; immunolocalization studies; knock-out mice; mGluR6; retina

PMID:
25997951
PMCID:
PMC4733627
DOI:
10.1111/ejn.12959
[Indexed for MEDLINE]
Free PMC Article

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