Publication Date:
2015-12-04
Description:
Somatic stem cells maintain tissue homeostasis by dynamically adjusting proliferation and differentiation in response to stress and metabolic cues. Here we identify Ca(2+) signalling as a central regulator of intestinal stem cell (ISC) activity in Drosophila. We show that dietary L-glutamate stimulates ISC division and gut growth. The metabotropic glutamate receptor (mGluR) is required in ISCs for this response, and for an associated modulation of cytosolic Ca(2+) oscillations that results in sustained high cytosolic Ca(2+) concentrations. High cytosolic Ca(2+) concentrations induce ISC proliferation by regulating Calcineurin and CREB-regulated transcriptional co-activator (Crtc). In response to a wide range of dietary and stress stimuli, ISCs reversibly transition between Ca(2+) oscillation states that represent poised or activated modes of proliferation, respectively. We propose that the dynamic regulation of intracellular Ca(2+) levels allows effective integration of diverse mitogenic signals in ISCs to adapt their proliferative activity to the needs of the tissue.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669953/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669953/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deng, Hansong -- Gerencser, Akos A -- Jasper, Heinrich -- R01 AG028127/AG/NIA NIH HHS/ -- R01 GM100196/GM/NIGMS NIH HHS/ -- S10 OD010414/OD/NIH HHS/ -- S10OD010414/OD/NIH HHS/ -- England -- Nature. 2015 Dec 10;528(7581):212-7. doi: 10.1038/nature16170. Epub 2015 Dec 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, California 94945, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26633624" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Calcium/*metabolism
;
Cell Proliferation/drug effects
;
Cytosol/chemistry
;
Diet
;
Drosophila melanogaster/*cytology/drug effects/metabolism
;
Glutamic Acid/pharmacology
;
Intestines/cytology
;
Receptors, Metabotropic Glutamate/metabolism
;
*Signal Transduction
;
Stem Cells/*cytology/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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