The Dunce cAMP phosphodiesterase PDE-4 negatively regulates G alpha(s)-dependent and G alpha(s)-independent cAMP pools in the Caenorhabditis elegans synaptic signaling network.

Genetics
Nicole K CharlieKenneth G Miller

Abstract

Forward genetic screens for mutations that rescue the paralysis of ric-8 (Synembryn) reduction-of-function mutations frequently reveal mutations that cause hyperactivation of one or more components of the G alpha(s) pathway. Here, we report that one of these mutations strongly reduces the function of the Dunce cAMP phosphodiesterase PDE-4 by disrupting a conserved active site residue. Loss of function and neural overexpression of PDE-4 have profound and opposite effects on locomotion rate, but drug-response assays suggest that loss of PDE-4 function does not affect steady-state acetylcholine release or reception. Our genetic analysis suggests that PDE-4 regulates both G alpha(s)-dependent and G alpha(s)-independent cAMP pools in the neurons controlling locomotion rate. By immunostaining, PDE-4 is strongly expressed throughout the nervous system, where it localizes to small regions at the outside boundaries of synaptic vesicle clusters as well as intersynaptic regions. The synaptic subregions containing PDE-4 are distinct from those containing active zones, as indicated by costaining with an antibody against the long form of UNC-13. This highly focal subsynaptic localization suggests that PDE-4 may exert its effects by spatially...Continue Reading

References

Jul 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·I N Maruyama, S Brenner
May 1, 1974·Genetics·S Brenner
Jan 1, 1996·Annual Review of Pharmacology and Toxicology·R K SunaharaA G Gilman
Nov 26, 1996·Proceedings of the National Academy of Sciences of the United States of America·C H BaileyE R Kandel
Jun 15, 1997·Genes & Development·H C KorswagenR H Plasterk
Oct 20, 1999·Nature Neuroscience·J E RichmondE M Jorgensen
Oct 20, 1999·Nature Neuroscience·B AravamudanK Broadie
Feb 12, 2000·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·E R Kandel, C Pittenger
Sep 13, 2000·The Journal of Biological Chemistry·M E HatleyR K Sunahara
Oct 12, 2000·Molecular Biology of the Cell·R E KohnJ B Rand
May 15, 2001·American Journal of Physiology. Cell Physiology·J S DuerrJ B Rand
Jul 17, 2001·Genetics·W J WolfgangM Forte
Sep 18, 2001·Nature Neuroscience·S P KoushikaM L Nonet
Jul 5, 2002·Genome Research·Kathryn A SwanMichael R Cancilla
Sep 17, 2002·EMBO Reports·Yoshishige KimuraHiroshi Tokumitsu
Jan 2, 2003·The Journal of Biological Chemistry·Gregory G TallAlfred G Gilman
Aug 28, 2003·Médecine sciences : M/S·Christelle Gally, Jean-Louis Bessereau

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Citations

Nov 18, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Pengxiu CaoZhaoyang Feng
Oct 19, 2007·Genes & Development·Stacey L WilliamsKenneth G Miller
Aug 9, 2008·PLoS Biology·Stacey L EdwardsKenneth G Miller
Mar 6, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Anindya Ghosh-RoyAndrew D Chisholm
Dec 1, 2010·Genetics·Rosana MesaMichael L Nonet
Apr 5, 2014·Neuron·Michael AilionErik M Jorgensen
Oct 3, 2009·The Journal of Cell Biology·Stacey L EdwardsKenneth G Miller
Apr 15, 2016·Proceedings of the National Academy of Sciences of the United States of America·Samuel H ChungChristopher V Gabel
Apr 17, 2015·BMC Developmental Biology·Boanerges Aleman-MezaWeiwei Zhong
Feb 7, 2017·Current Biology : CB·Wagner Steuer CostaAlexander Gottschalk
Aug 10, 2006·Cell and Tissue Research·Mark SeifertRalf Baumeister
May 10, 2007·Nature Protocols·Timothy R MahoneyMichael L Nonet
Jan 11, 2008·Nature·David M RaizenAllan I Pack
Apr 30, 2011·Physiological Reviews·Sharron H FrancisJackie D Corbin
Oct 13, 2020·Journal of Neurogenetics·Madison HonerMatthew D Nelson
Dec 4, 2021·Neuron·Jesus Fernandez-AbascalLaura Bianchi

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