The presynaptic glycine transporter GlyT2 is regulated by the Hedgehog pathway in vitro and in vivo

Autor: Jaime de Juan-Sanz, Anjali Amrapali Vishwanath, Andrés de la Rocha-Muñoz, Beatriz López-Corcuera, Carmen Aragón, Dhanasak Dhanasobhon, Nelson Rebola, Enrique Núñez, Sergio Gomez-Lopez
Přispěvatelé: Universidad Autónoma de Madrid (UAM), Hospital Universitario La Paz, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centro de Biología Molecular Severo Ochoa [Madrid] (CBMSO), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), HAL-SU, Gestionnaire, UAM. Departamento de Biología Molecular, Universidad Autonoma de Madrid (UAM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Ministerio de Economía y Competitividad (España), Fundación Ramón Areces, Banco Santander
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Embryo
Nonmammalian
Glycine Transporter
[SDV]Life Sciences [q-bio]
Wistar
Medicine (miscellaneous)
Glycine transporter
0302 clinical medicine
Glycine Plasma Membrane Transport Proteins
Hyperekplexia
Biology (General)
Transporters in the nervous system
Glycine receptor
Zebrafish
0303 health sciences
Sonic Hedgehog Protein
Nonmammalian
Chemistry
SLC6A5 Protein
Biología y Biomedicina / Biología
Hedgehog signaling pathway
3. Good health
Cell biology
[SDV] Life Sciences [q-bio]
Embryo
embryonic structures
Zebrafish Protein
medicine.symptom
General Agricultural and Biological Sciences
Signal Transduction
animal structures
QH301-705.5
Neurotransmission
General Biochemistry
Genetics and Molecular Biology
Article
03 medical and health sciences
medicine
Animals
Hedgehog Proteins
Rats
Wistar
Hedgehog
030304 developmental biology
Zebrafish Proteins
Cellular neuroscience
Rats
Metabolism
Glycine
Rat
Glycinergic synapse
030217 neurology & neurosurgery
Zdroj: Communications Biology
Communications Biology, 2021, 4 (1), ⟨10.1038/s42003-021-02718-6⟩
Communications Biology, Nature Publishing Group, 2021, 4 (1), ⟨10.1038/s42003-021-02718-6⟩
Communications Biology, Vol 4, Iss 1, Pp 1-10 (2021)
Digital.CSIC. Repositorio Institucional del CSIC
instname
Biblos-e Archivo. Repositorio Institucional de la UAM
ISSN: 2399-3642
DOI: 10.1038/s42003-021-02718-6⟩
Popis: The identity of a glycinergic synapse is maintained presynaptically by the activity of a surface glycine transporter, GlyT2, which recaptures glycine back to presynaptic terminals to preserve vesicular glycine content. GlyT2 loss-of-function mutations cause Hyperekplexia, a rare neurological disease in which loss of glycinergic neurotransmission causes generalized stiffness and strong motor alterations. However, the molecular underpinnings controlling GlyT2 activity remain poorly understood. In this work, we identify the Hedgehog pathway as a robust controller of GlyT2 expression and transport activity. Modulating the activation state of the Hedgehog pathway in vitro in rodent primary spinal cord neurons or in vivo in zebrafish embryos induced a selective control in GlyT2 expression, regulating GlyT2 transport activity. Our results indicate that activation of Hedgehog reduces GlyT2 expression by increasing its ubiquitination and degradation. This work describes a new molecular link between the Hedgehog signaling pathway and presynaptic glycine availability.
By modulating the activation state of the Hedgehog pathway, de la Rocha-Muñoz et al demonstrate that Hedgehog signaling controls the expression and transport activity of the neuronal glycine transporter GlyT2. This work begins to reveal a potential link between the Hedgehog signaling pathway and presynaptic glycine availability.
Databáze: OpenAIRE
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