title: Signal integration by Ca(2+) regulates intestinal stem-cell activity.
abstract: 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.
authors.affiliation: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, California 94945, USA.
authors.forename: Hansong
authors.initials: H
authors.lastname: Deng
authors.affiliation: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, California 94945, USA.
authors.forename: Akos A
authors.initials: AA
authors.lastname: Gerencser
authors.affiliation: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, California 94945, USA.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Jasper
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D003600:Cytosol / Q000737:chemistry; D004032:Diet; D004331:Drosophila melanogaster / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D007422:Intestines / Q000166:cytology; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; D002118:Calcium