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AWD regulates timed activation of BMP signaling in intestinal stem cells to maintain tissue homeostasis
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AWD regulates timed activation of BMP signaling in intestinal stem cells to maintain tissue homeostasis
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Journal Article
AWD regulates timed activation of BMP signaling in intestinal stem cells to maintain tissue homeostasis
2019
Overview
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.
Regeneration after injury in the Drosophila intestine involves early activation of intestinal stem cells (ISCs) and subsequent return to quiescence. Here the authors show that return to quiescence by ISCs involves BMP Type I receptor Tkv protein stabilization along with AWD mediated internalization into endocytic vesicles.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/51
/ 64/24
/ Animals
/ Bone Morphogenetic Proteins - metabolism
/ DNA-Binding Proteins - metabolism
/ Drosophila Proteins - metabolism
/ Female
/ Humanities and Social Sciences
/ Kinases
/ Nerve Tissue Proteins - metabolism
/ Nucleoside-diphosphate kinase
/ Nucleoside-Diphosphate Kinase - metabolism
/ Protein-Serine-Threonine Kinases - metabolism
/ Proteins
/ Receptors, Cell Surface - metabolism
/ Science
/ Signal Transduction - physiology
