Ptch2/Gas1 and Ptch1/Boc differentially regulate Hedgehog signalling in murine primordial germ cell migration.

3T3 Cells Animals Cell Cycle Proteins / genetics Chemotaxis / genetics Cyclic AMP Response Element-Binding Protein / metabolism Embryo, Mammalian Female GPI-Linked Proteins / genetics Gene Expression Regulation, Developmental Gene Knockout Techniques Germ Cells / physiology Hedgehog Proteins / metabolism Immunoglobulin G / metabolism Intravital Microscopy Male Mice Mice, Transgenic Organ Culture Techniques Patched-1 Receptor / genetics Patched-2 Receptor / metabolism Receptors, Cell Surface / metabolism Signal Transduction / genetics Smoothened Receptor / metabolism Time-Lapse Imaging src-Family Kinases / metabolism

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
24 04 2020
Historique:
received: 24 08 2019
accepted: 01 04 2020
entrez: 26 4 2020
pubmed: 26 4 2020
medline: 11 8 2020
Statut: epublish

Résumé

Gas1 and Boc/Cdon act as co-receptors in the vertebrate Hedgehog signalling pathway, but the nature of their interaction with the primary Ptch1/2 receptors remains unclear. Here we demonstrate, using primordial germ cell migration in mouse as a developmental model, that specific hetero-complexes of Ptch2/Gas1 and Ptch1/Boc mediate the process of Smo de-repression with different kinetics, through distinct modes of Hedgehog ligand reception. Moreover, Ptch2-mediated Hedgehog signalling induces the phosphorylation of Creb and Src proteins in parallel to Gli induction, identifying a previously unknown Ptch2-specific signal pathway. We propose that although Ptch1 and Ptch2 functionally overlap in the sequestration of Smo, the spatiotemporal expression of Boc and Gas1 may determine the outcome of Hedgehog signalling through compartmentalisation and modulation of Smo-downstream signalling. Our study identifies the existence of a divergent Hedgehog signal pathway mediated by Ptch2 and provides a mechanism for differential interpretation of Hedgehog signalling in the germ cell niche.

Identifiants

DOI: 10.1038/s41467-020-15897-3 PMID: 32332736 PMC: PMC7181751
pubmed: 32332736
doi: 10.1038/s41467-020-15897-3
pii: 10.1038/s41467-020-15897-3
pmc: PMC7181751
doi:

Substances chimiques

Boc protein, mouse 0
Cell Cycle Proteins 0
Creb1 protein, mouse 0
Cyclic AMP Response Element-Binding Protein 0
GPI-Linked Proteins 0
Gas1 protein, mouse 0
Hedgehog Proteins 0
Immunoglobulin G 0
Patched-1 Receptor 0
Patched-2 Receptor 0
Ptch1 protein, mouse 0
Ptch2 protein, mouse 0
Receptors, Cell Surface 0
Shh protein, mouse 0
Smo protein, mouse 0
Smoothened Receptor 0
src-Family Kinases EC 2.7.10.2

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1994

Subventions

Organisme : Medical Research Council
ID : MR/L020378/1
Pays : United Kingdom

Commentaires et corrections

Type : ErratumIn

Références

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Auteurs

Yeonjoo Kim (Y)

Molecular and Clinical Sciences Research Institute, St. George's, University of London, Cranmer Terrace, London, SW17 0RE, UK.
ORCID: 0000-0001-8896-1153

Jiyoung Lee (J)

Molecular and Clinical Sciences Research Institute, St. George's, University of London, Cranmer Terrace, London, SW17 0RE, UK.

Maisa Seppala (M)

Centre for Craniofacial and Regenerative Biology, Faculty of Dental, Oral and Craniofacial Sciences King's College London Floor 27, Guy's Hospital, London, SE1 9RT, UK.
ORCID: 0000-0001-6806-1318

Martyn T Cobourne (MT)

Centre for Craniofacial and Regenerative Biology, Faculty of Dental, Oral and Craniofacial Sciences King's College London Floor 27, Guy's Hospital, London, SE1 9RT, UK.
ORCID: 0000-0003-2857-0315

Soo-Hyun Kim (SH)

Molecular and Clinical Sciences Research Institute, St. George's, University of London, Cranmer Terrace, London, SW17 0RE, UK. skim@sgul.ac.uk.
ORCID: 0000-0002-9394-1437

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Classifications MeSH

questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Fibroblastes › Cellules 3T3 › Ptch2/Gas1 and Ptch1/Boc differentially...
questionsmedicales.fr › Eucaryotes › Animaux › Ptch2/Gas1 and Ptch1/Boc differentially...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cycle cellulaire › Ptch2/Gas1 and Ptch1/Boc differentially...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système locomoteur › Mouvement › Locomotion › Taxie › Chimiotaxie › Ptch2/Gas1 and Ptch1/Boc differentially...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique et à glissière à leucines › Protéine de liaison à l'élément de réponse à l'AMP cyclique › Ptch2/Gas1 and Ptch1/Boc differentially...
questionsmedicales.fr › Structures de l'embryon › Embryon de mammifère › Ptch2/Gas1 and Ptch1/Boc differentially...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Glycoprotéines membranaires › Protéines liées au GPI › Ptch2/Gas1 and Ptch1/Boc differentially...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes au cours du développement › Ptch2/Gas1 and Ptch1/Boc differentially...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Ciblage de gène › Techniques de knock-out de gènes › Ptch2/Gas1 and Ptch1/Boc differentially...
questionsmedicales.fr › Cellules › Cellules germinales › Ptch2/Gas1 and Ptch1/Boc differentially...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines Hedgehog › Ptch2/Gas1 and Ptch1/Boc differentially...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Isotypes des immunoglobulines › Immunoglobuline G › Ptch2/Gas1 and Ptch1/Boc differentially...
questionsmedicales.fr › Techniques d'investigation › Microscopie intravitale › Ptch2/Gas1 and Ptch1/Boc differentially...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Ptch2/Gas1 and Ptch1/Boc differentially...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Ptch2/Gas1 and Ptch1/Boc differentially...
questionsmedicales.fr › Techniques d'investigation › Techniques in vitro › Techniques de culture › Techniques de culture d'organes › Ptch2/Gas1 and Ptch1/Boc differentially...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Récepteurs patched › Récepteur Patched-1 › Ptch2/Gas1 and Ptch1/Boc differentially...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Récepteurs patched › Récepteur Patched-2 › Ptch2/Gas1 and Ptch1/Boc differentially...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Ptch2/Gas1 and Ptch1/Boc differentially...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Ptch2/Gas1 and Ptch1/Boc differentially...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs Wnt › Récepteurs Frizzled › Récepteur Smoothened › Ptch2/Gas1 and Ptch1/Boc differentially...
questionsmedicales.fr › Sciences de l'information › Processus de copie › Enregistrement sur magnétoscope › Imagerie accélérée › Ptch2/Gas1 and Ptch1/Boc differentially...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-tyrosine kinases › src-Family kinases › Ptch2/Gas1 and Ptch1/Boc differentially...