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

Marion Neuillé, Catherine Morgans, Yan Cao, Elise Orhan, Christelle Michiels, José Alain Sahel, Isabelle Audo, Robert Duvoisin, Kirill A. Martemyanov, Christina Zeitz

Research output: Contribution to journalArticle

15 Citations (Scopus)

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, (Lrit3nob6/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 Lrit3nob6/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 Lrit3nob6/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 Lrit3nob6/nob6 mice. mGluR6, GPR179, RGS7, RGS11 and Gβ5 immunofluorescence was absent at the dendritic tips of cone ON-bipolar cells in Lrit3nob6/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 Lrit3nob6/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.

Original languageEnglish (US)
Pages (from-to)1966-1975
Number of pages10
JournalEuropean Journal of Neuroscience
Volume42
Issue number3
DOIs
StatePublished - Aug 1 2015

Fingerprint

Synapses
Peanut Agglutinin
Staining and Labeling
Calbindins
Mutation
Vertebrate Photoreceptor Cells
Fluorescence Microscopy
Confocal Microscopy
Fluorescent Antibody Technique
Retina
Anti-Idiotypic Antibodies
metabotropic glutamate receptor 6

Keywords

  • Complete CSNB
  • Immunolocalization studies
  • Knock-out mice
  • mGluR6
  • Retina

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

LRIT3 is essential to localize TRPM1 to the dendritic tips of depolarizing bipolar cells and may play a role in cone synapse formation. / Neuillé, Marion; Morgans, Catherine; Cao, Yan; Orhan, Elise; Michiels, Christelle; Sahel, José Alain; Audo, Isabelle; Duvoisin, Robert; Martemyanov, Kirill A.; Zeitz, Christina.

In: European Journal of Neuroscience, Vol. 42, No. 3, 01.08.2015, p. 1966-1975.

Research output: Contribution to journalArticle

Neuillé, Marion ; Morgans, Catherine ; Cao, Yan ; Orhan, Elise ; Michiels, Christelle ; Sahel, José Alain ; Audo, Isabelle ; Duvoisin, Robert ; Martemyanov, Kirill A. ; Zeitz, Christina. / LRIT3 is essential to localize TRPM1 to the dendritic tips of depolarizing bipolar cells and may play a role in cone synapse formation. In: European Journal of Neuroscience. 2015 ; Vol. 42, No. 3. pp. 1966-1975.
@article{27d29aef52b44573af208d505742ca20,
title = "LRIT3 is essential to localize TRPM1 to the dendritic tips of depolarizing bipolar cells and may play a role in cone synapse formation",
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, (Lrit3nob6/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 Lrit3nob6/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 Lrit3nob6/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 Lrit3nob6/nob6 mice. mGluR6, GPR179, RGS7, RGS11 and Gβ5 immunofluorescence was absent at the dendritic tips of cone ON-bipolar cells in Lrit3nob6/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 Lrit3nob6/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",
author = "Marion Neuill{\'e} and Catherine Morgans and Yan Cao and Elise Orhan and Christelle Michiels and Sahel, {Jos{\'e} Alain} and Isabelle Audo and Robert Duvoisin and Martemyanov, {Kirill A.} and Christina Zeitz",
year = "2015",
month = "8",
day = "1",
doi = "10.1111/ejn.12959",
language = "English (US)",
volume = "42",
pages = "1966--1975",
journal = "European Journal of Neuroscience",
issn = "0953-816X",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - LRIT3 is essential to localize TRPM1 to the dendritic tips of depolarizing bipolar cells and may play a role in cone synapse formation

AU - Neuillé, Marion

AU - Morgans, Catherine

AU - Cao, Yan

AU - Orhan, Elise

AU - Michiels, Christelle

AU - Sahel, José Alain

AU - Audo, Isabelle

AU - Duvoisin, Robert

AU - Martemyanov, Kirill A.

AU - Zeitz, Christina

PY - 2015/8/1

Y1 - 2015/8/1

N2 - 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, (Lrit3nob6/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 Lrit3nob6/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 Lrit3nob6/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 Lrit3nob6/nob6 mice. mGluR6, GPR179, RGS7, RGS11 and Gβ5 immunofluorescence was absent at the dendritic tips of cone ON-bipolar cells in Lrit3nob6/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 Lrit3nob6/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.

AB - 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, (Lrit3nob6/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 Lrit3nob6/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 Lrit3nob6/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 Lrit3nob6/nob6 mice. mGluR6, GPR179, RGS7, RGS11 and Gβ5 immunofluorescence was absent at the dendritic tips of cone ON-bipolar cells in Lrit3nob6/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 Lrit3nob6/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.

KW - Complete CSNB

KW - Immunolocalization studies

KW - Knock-out mice

KW - mGluR6

KW - Retina

UR - http://www.scopus.com/inward/record.url?scp=84938286345&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938286345&partnerID=8YFLogxK

U2 - 10.1111/ejn.12959

DO - 10.1111/ejn.12959

M3 - Article

VL - 42

SP - 1966

EP - 1975

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

IS - 3

ER -