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Ion transporter NKCC1, modulator of neurogenesis in murine olfactory neurons

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Item Type:Article
Title:Ion transporter NKCC1, modulator of neurogenesis in murine olfactory neurons
Creators Name:Haering, C. and Kanageswaran, N. and Bouvain, P. and Scholz, P. and Altmüller, J. and Becker, C. and Gisselmann, G. and Wäring-Bischof, J. and Hatt, H.
Abstract:BACKGROUND: NKCC1 is controversially discussed as the main chloride transporter in olfactory epithelium. RESULTS: Lack of NKCC1 results in impaired odorant detection and a decrease in the number of mature neurons. CONCLUSION: NKCC1 is involved in chloride accumulation but also reveals an impact in neurogenesis. SIGNIFICANCE: This work contributes to the understanding of olfactory epithelium neurogenesis. Olfaction is one of the most crucial senses for vertebrates regarding foraging and social behavior. Therefore, it is of particular interest to investigate the sense of smell, its function on a molecular level, the signaling proteins involved in the process and the mechanism of required ion transport. In recent years, the precise role of the ion transporter NKCC1 in olfactory sensory neuron (OSN) chloride accumulation has been a controversial subject. NKCC1 is expressed in OSNs and is involved in chloride accumulation of dissociated neurons, but it had not been shown to play a role in mouse odorant sensation. Here, we present electro-olfactogram recordings (EOG) demonstrating that NKCC1-deficient mice exhibit significant defects in perception of a complex odorant mixture (Henkel100) in both air-phase and submerged approaches. Using next generation sequencing (NGS) and RT-PCR experiments of NKCC1-deficient and wild type mouse transcriptomes, we confirmed the absence of a highly expressed ion transporter that could compensate for NKCC1. Additional histological investigations demonstrated a reduced number of cells in the olfactory epithelium (OE), resulting in a thinner neuronal layer. Therefore, we conclude that NKCC1 is an important transporter involved in chloride ion accumulation in the olfactory epithelium, but it is also involved in OSN neurogenesis.
Keywords:Development, Electrophysiology, Na-K-Cl Cotransporter (NKCC), Neurobiology, Neurogenesis, NKCC1, Olfaction, Chloride, Knockout Mouse, Next Generation Sequencing, Animals, Mice
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology
Volume:290
Number:15
Page Range:9767-9779
Date:4 January 2021
Official Publication:https://doi.org/10.1074/jbc.M115.640656
PubMed:View item in PubMed

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