An insulin-dependent neuro-endocrine signal targets PTEN, LKB1 and AMPK to regulate germline stem cell quiescence. Export

@inproceedings{citeulike:3333687, abstract = { During adverse environmental conditions, the signaling level of any of three parallel pathways (cGMP, TGF-<font face=symbol>b</font>, or insulin) can induce C. elegans larvae to enter a diapause-like stage called dauer. All three pathways converge to regulate the production of a sterol-related molecule that binds the nuclear hormone receptor DAF-12 and thereby stimulates reproductive development. When any one of these pathways is down-regulated, the hormone is no longer secreted, and DAF-12 induces dauer formation. Dauer development is tightly associated with the progressive establishment and maintenance of cell cycle quiescence throughout the animal during the extended pre-dauer (L2d) stage. In the germline stem cell population, dauer-dependent quiescence cell autonomously requires the activity of the two AMPK catalytic subunit isoforms, aak-1 and aak-2. To fulfill this role, aak-1/2 further require, at least in part, the activity of par-4/LKB1 (an AMPK-activating kinase), strd-1/STRAD (an LKB1 co-factor) and of aakb-2, which is the primary AMPK <font face=symbol>b</font> regulatory subunit used to establish germline quiescence. The insulin signaling cascade, from the receptor daf-2 down to the transcription factor daf-16, functions in neurons to regulate this developmental switch. We observe that neuronal daf-16 activity is also sufficient to down-regulate germline proliferation during dauer development. This is unlikely to occur solely through DAF-12 regulation because daf-2; daf-12 mutants, despite the fact that they do not form dauers, grow into sterile adults with underdeveloped germlines typical of daf-2 animals. Interestingly, neuronal daf-18/PTEN (an intermediate player in the insulin cascade) is not sufficient to rescue germline quiescence in daf-2; daf-18 or daf-7; daf-18 mutants, and in fact functions cell autonomously in the germline to block proliferation, in addition to its critical function in the neuronal cascade involved in dauer formation. We therefore propose a model where a daf-12 independent insulin-regulated signal is produced in the nervous system and targets daf-18, par-4 and aak-1/2 in the germline to regulate proliferation of the stem cell population during dauer development. Our epistasis analysis suggests that aak-2 requires daf-18 for function, while par-4 works, at least in part independently of daf-18, through aak-1 and yet unidentified gene(s).}, author = {Narbonne, Patrick and Richard, Roy}, citeulike-article-id = {3333687}, citeulike-linkout-0 = {http://www.wormbase.org/db/misc/paper?name=WBPaper00030570}, journal = {International Worm Meeting}, keywords = {aak-1, aak-2, aakb-2, b04122, c\_elegans, caenorhabditis\_elegans, celegans, daf-12, daf-16, daf-18, daf-2, daf-7, elegans, f11a13, meeting\_abstract, nematode, par-4, par23, r13h81, t01c81, t07a96, wormbase, y47d3a15, y55d5a5, y59a8b14}, posted-at = {2008-09-24 20:14:14}, priority = {3}, title = {An insulin-dependent neuro-endocrine signal targets PTEN, LKB1 and AMPK to regulate germline stem cell quiescence.}, url = {http://www.wormbase.org/db/misc/paper?name=WBPaper00030570}, year = {2007} }

TY - CONF ID - citeulike:3333687 L3 - citeulike-article-id:3333687 N2 - During adverse environmental conditions, the signaling level of any of three parallel pathways (cGMP, TGF-<font face=symbol>b</font>, or insulin) can induce C. elegans larvae to enter a diapause-like stage called dauer. All three pathways converge to regulate the production of a sterol-related molecule that binds the nuclear hormone receptor DAF-12 and thereby stimulates reproductive development. When any one of these pathways is down-regulated, the hormone is no longer secreted, and DAF-12 induces dauer formation. Dauer development is tightly associated with the progressive establishment and maintenance of cell cycle quiescence throughout the animal during the extended pre-dauer (L2d) stage. In the germline stem cell population, dauer-dependent quiescence cell autonomously requires the activity of the two AMPK catalytic subunit isoforms, aak-1 and aak-2. To fulfill this role, aak-1/2 further require, at least in part, the activity of par-4/LKB1 (an AMPK-activating kinase), strd-1/STRAD (an LKB1 co-factor) and of aakb-2, which is the primary AMPK <font face=symbol>b</font> regulatory subunit used to establish germline quiescence. The insulin signaling cascade, from the receptor daf-2 down to the transcription factor daf-16, functions in neurons to regulate this developmental switch. We observe that neuronal daf-16 activity is also sufficient to down-regulate germline proliferation during dauer development. This is unlikely to occur solely through DAF-12 regulation because daf-2; daf-12 mutants, despite the fact that they do not form dauers, grow into sterile adults with underdeveloped germlines typical of daf-2 animals. Interestingly, neuronal daf-18/PTEN (an intermediate player in the insulin cascade) is not sufficient to rescue germline quiescence in daf-2; daf-18 or daf-7; daf-18 mutants, and in fact functions cell autonomously in the germline to block proliferation, in addition to its critical function in the neuronal cascade involved in dauer formation. We therefore propose a model where a daf-12 independent insulin-regulated signal is produced in the nervous system and targets daf-18, par-4 and aak-1/2 in the germline to regulate proliferation of the stem cell population during dauer development. Our epistasis analysis suggests that aak-2 requires daf-18 for function, while par-4 works, at least in part independently of daf-18, through aak-1 and yet unidentified gene(s). JF - International Worm Meeting TI - An insulin-dependent neuro-endocrine signal targets PTEN, LKB1 and AMPK to regulate germline stem cell quiescence. KW - aak-1 KW - aak-2 KW - aakb-2 KW - b04122 KW - c_elegans KW - caenorhabditis_elegans KW - celegans KW - daf-12 KW - daf-16 KW - daf-18 KW - daf-2 KW - daf-7 KW - elegans KW - f11a13 KW - meeting_abstract KW - nematode KW - par-4 KW - par23 KW - r13h81 KW - t01c81 KW - t07a96 KW - wormbase KW - y47d3a15 KW - y55d5a5 KW - y59a8b14 AU - Narbonne, Patrick AU - Richard, Roy PY - 2007/// UR - http://www.wormbase.org/db/misc/paper?name=WBPaper00030570 ER -