AWD regulates timed activation of BMP signaling in intestinal stem cells to maintain tissue homeostasis.
Animals
Bone Morphogenetic Proteins
/ metabolism
DNA-Binding Proteins
/ metabolism
Drosophila Proteins
/ metabolism
Drosophila melanogaster
Female
Homeostasis
/ physiology
Intestines
/ cytology
Models, Animal
Nerve Tissue Proteins
/ metabolism
Nucleoside-Diphosphate Kinase
/ metabolism
Protein Serine-Threonine Kinases
/ metabolism
Receptors, Cell Surface
/ metabolism
Regeneration
Signal Transduction
/ physiology
Stem Cells
/ metabolism
Transcription Factors
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
05 07 2019
05 07 2019
Historique:
received:
17
10
2018
accepted:
06
06
2019
entrez:
7
7
2019
pubmed:
7
7
2019
medline:
23
10
2019
Statut:
epublish
Résumé
Precise control of stem cell (SC) proliferation ensures tissue homeostasis. In the Drosophila intestine, injury-induced regeneration involves initial activation of intestinal SC (ISC) proliferation and subsequent return to quiescence. These two phases of the regenerative response are controlled by differential availability of the BMP type I receptor Thickveins (Tkv), yet how its expression is dynamically regulated remains unclear. Here we show that during homeostasis, the E3 ubiquitin ligase Highwire and the ubiquitin-proteasome system maintain low Tkv protein expression. After ISC activation, Tkv is stabilized by proteasome inhibition and undergoes endocytosis due to the induction of the nucleoside diphosphate kinase Abnormal Wing Disc (AWD). Tkv internalization is required for the activation of the Smad protein Mad, and for the return to quiescence after a regenerative episode. Our data provide insight into the mechanisms ensuring tissue homeostasis by dynamic control of somatic stem cell activity.
Identifiants
pubmed: 31278345
doi: 10.1038/s41467-019-10926-2
pii: 10.1038/s41467-019-10926-2
pmc: PMC6611797
doi:
Substances chimiques
Bone Morphogenetic Proteins
0
DNA-Binding Proteins
0
Drosophila Proteins
0
HIW protein, Drosophila
0
MAD protein, Drosophila
0
Nerve Tissue Proteins
0
Receptors, Cell Surface
0
Transcription Factors
0
tkv protein, Drosophila
EC 2.7.1.-
Protein Serine-Threonine Kinases
EC 2.7.11.1
Nucleoside-Diphosphate Kinase
EC 2.7.4.6
awd protein, Drosophila
EC 2.7.4.6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2988Subventions
Organisme : Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie (Federal Ministry for Education, Science, Research and Technology)
ID : EXC294
Pays : International
Organisme : NIA NIH HHS
ID : R01 AG050104
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : GM117412
Pays : International
Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
ID : AG050104
Pays : International
Organisme : NIGMS NIH HHS
ID : R01 GM117412
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG047497
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
ID : AG047497
Pays : International
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : PY72/2-1
Pays : International
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