Boc Acts via Numb as a Shh-Dependent Endocytic Platform for Ptch1 Internalization and Shh-Mediated Axon Guidance.

Animals Axon Guidance / genetics Endocytosis / genetics Gene Knockdown Techniques Growth Cones / metabolism Hedgehog Proteins / metabolism Immunoglobulin G / metabolism Membrane Proteins / genetics Mice Nerve Tissue Proteins / genetics Neurons / metabolism Patched-1 Receptor / metabolism Receptors, Cell Surface / metabolism
Boc Numb Patched1 axon guidance commissural neurons endocytosis sonic hedgehog

Journal

Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320

Informations de publication

Date de publication:
19 06 2019
Historique:
received: 14 08 2018
revised: 08 02 2019
accepted: 28 03 2019
pubmed: 6 5 2019
medline: 24 3 2020
entrez: 6 5 2019
Statut: ppublish

Résumé

During development, Shh attracts commissural axons toward the floor plate through a non-canonical, transcription-independent signaling pathway that requires the receptor Boc. Here, we find that Shh induces Boc internalization into early endosomes and that endocytosis is required for Shh-mediated growth-cone turning. Numb, an endocytic adaptor, binds to Boc and is required for Boc internalization, Shh-mediated growth-cone turning in vitro, and commissural axon guidance in vivo. Similar to Boc, Ptch1 is also internalized by Shh in a Numb-dependent manner; however, the binding of Shh to Ptch1 alone is not sufficient to induce Ptch1 internalization nor growth-cone turning. Therefore, the binding of Shh to Boc is required for Ptch1 internalization and growth-cone turning. Our data support a model where Boc endocytosis via Numb is required for Ptch1 internalization and Shh signaling in axon guidance. Thus, Boc acts as a Shh-dependent endocytic platform gating Ptch1 internalization and Shh signaling.

Identifiants

DOI: 10.1016/j.neuron.2019.04.003 PMID: 31054872
pubmed: 31054872
pii: S0896-6273(19)30338-1
doi: 10.1016/j.neuron.2019.04.003
pii:
doi:

Substances chimiques

Boc protein, mouse 0
Hedgehog Proteins 0
Immunoglobulin G 0
Membrane Proteins 0
Nerve Tissue Proteins 0
Numb protein, mouse 0
Patched-1 Receptor 0
Ptch1 protein, mouse 0
Receptors, Cell Surface 0
Shh protein, mouse 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Video-Audio Media

Langues

eng

Sous-ensembles de citation

IM

Pagination

1157-1171.e5

Subventions

Organisme : CIHR
ID : FDN334023
Pays : Canada

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

Auteurs

Julien Ferent (J)

Montreal Clinical Research Institute (IRCM), 110 Pine Avenue West, Montreal, QC H2W 1R7, Canada; Department of Neuroscience, University of Montreal, Montreal, QC H3T 1J4, Canada.

Fanny Giguère (F)

Montreal Clinical Research Institute (IRCM), 110 Pine Avenue West, Montreal, QC H2W 1R7, Canada.

Christine Jolicoeur (C)

Montreal Clinical Research Institute (IRCM), 110 Pine Avenue West, Montreal, QC H2W 1R7, Canada.

Steves Morin (S)

Montreal Clinical Research Institute (IRCM), 110 Pine Avenue West, Montreal, QC H2W 1R7, Canada.

Jean-Francois Michaud (JF)

Montreal Clinical Research Institute (IRCM), 110 Pine Avenue West, Montreal, QC H2W 1R7, Canada.

Shirin Makihara (S)

Montreal Clinical Research Institute (IRCM), 110 Pine Avenue West, Montreal, QC H2W 1R7, Canada.

Patricia T Yam (PT)

Montreal Clinical Research Institute (IRCM), 110 Pine Avenue West, Montreal, QC H2W 1R7, Canada.

Michel Cayouette (M)

Montreal Clinical Research Institute (IRCM), 110 Pine Avenue West, Montreal, QC H2W 1R7, Canada; Department of Anatomy and Cell Biology, Division of Experimental Medicine, McGill University, Montreal, QC H3A 0G4, Canada; Department of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada.

Frederic Charron (F)

Montreal Clinical Research Institute (IRCM), 110 Pine Avenue West, Montreal, QC H2W 1R7, Canada; Department of Anatomy and Cell Biology, Division of Experimental Medicine, McGill University, Montreal, QC H3A 0G4, Canada; Department of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada; Department of Biology, McGill University, Montreal, QC H3A 0G4, Canada. Electronic address: frederic.charron@ircm.qc.ca.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Boc Acts via Numb as a Shh-Dependent Endocytic...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système nerveux › Neurogenèse › Excroissance neuronale › Guidage axonal › Boc Acts via Numb as a Shh-Dependent Endocytic...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Endocytose › Boc Acts via Numb as a Shh-Dependent Endocytic...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Ciblage de gène › Techniques de knock-down de gènes › Boc Acts via Numb as a Shh-Dependent Endocytic...
questionsmedicales.fr › Cellules › Neurones › Neurofibres › Axones › Cônes de croissance › Boc Acts via Numb as a Shh-Dependent Endocytic...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines Hedgehog › Boc Acts via Numb as a Shh-Dependent Endocytic...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Isotypes des immunoglobulines › Immunoglobuline G › Boc Acts via Numb as a Shh-Dependent Endocytic...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Boc Acts via Numb as a Shh-Dependent Endocytic...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Boc Acts via Numb as a Shh-Dependent Endocytic...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Boc Acts via Numb as a Shh-Dependent Endocytic...
questionsmedicales.fr › Cellules › Neurones › Boc Acts via Numb as a Shh-Dependent Endocytic...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Récepteurs patched › Récepteur Patched-1 › Boc Acts via Numb as a Shh-Dependent Endocytic...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Boc Acts via Numb as a Shh-Dependent Endocytic...