Mee, Christopher J., Pym, Edward C.G., Moffat, Kevin G. and Baines, Richard A.. (2004) Regulation of neuronal excitability through pumilio-dependent control of a sodium channel gene. Journal of Neuroscience, Vol.24 (No.40). pp. 8695-8703. ISSN 0270-6474

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Abstract

Dynamic changes in synaptic connectivity and strength, which occur during both embryonic development and learning, have the tendency to destabilize neural circuits. To overcome this, neurons have developed a diversity of homeostatic mechanisms to maintain firing within physiologically defined limits. In this study, we show that activity-dependent control of mRNA for a specific voltage-gated Na+ channel [encoded by paralytic (para)] contributes to the regulation of membrane excitability in Drosophila motoneurons. Quantification of para mRNA, by real-time reverse-transcription PCR, shows that levels are significantly decreased in CNSs in which synaptic excitation is elevated, whereas, conversely, they are significantly increased when synaptic vesicle release is blocked. Quantification of mRNA encoding the translational repressor pumilio (pum) reveals a reciprocal regulation to that seen for para. Pumilio is sufficient to influence para mRNA. Thus, para mRNA is significantly elevated in a loss-of-function allele of pum (pumbemused), whereas expression of a full-length pum transgene is sufficient to reduce para mRNA. In the absence of pum, increased synaptic excitation fails to reduce para mRNA, showing that Pum is also necessary for activity-dependent regulation of para mRNA. Analysis of voltage-gated Na+ current (INa) mediated by para in two identified motoneurons (termed aCC and RP2) reveals that removal of pum is sufficient to increase one of two separable INa components (persistent INa), whereas overexpression of a pum transgene is sufficient to suppress both components (transient and persistent). We show, through use of anemone toxin (ATX II), that alteration in persistent INa is sufficient to regulate membrane excitability in these two motoneurons.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry Q Science > QL Zoology
Divisions:	Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Library of Congress Subject Headings (LCSH):	Neuroplasticity -- Research, Synapses -- Research, Excitation (Physiology), Sodium channels, Drosophila -- Physiology
Journal or Publication Title:	Journal of Neuroscience
Publisher:	Society for Neuroscience
ISSN:	0270-6474
Date:	6 October 2004
Volume:	Vol.24
Number:	No.40
Page Range:	pp. 8695-8703
Identification Number:	10.1523/JNEUROSCI.2282-04.2004
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Funder:	Wellcome Trust (London, England)
References:	Alzheimer C (1994) A novel voltage-dependent cation current in rat neocortical neurones. J Physiol (Lond) 479:199–204. Antic D, Keene JD (1997) Embryonic lethal abnormal visual RNA-binding proteins involved in growth, differentiation, and post-transcriptional gene expression. Am J Hum Genet 61:273–278. Atasoy U, Watson J, Patel D, Keene JD (1998) ELAV protein HuA (HuR) can redistribute between nucleus and cytoplasm and is up-regulated during serum stimulation and T cell activation. J Cell Sci 111:3145–3156. Baines RA (2003) Postsynaptic protein kinase A reduces neuronal excitability in response to increased synaptic excitation in the Drosophila CNS. J Neurosci 23:8664–8672. Baines RA, BateM (1998) Electrophysiological development of central neurons in the Drosophila embryo. J Neurosci 18:4673–4683. Baines RA, Robinson SG, Fujioka M, Jaynes JB, BateM (1999) Postsynaptic vesicle release is essential for synaptogenesis in Drosophila. Curr Biol 9:1267–1270. Baines RA, Uhler JP, Thompson A, Sweeney ST, Bate M (2001) Altered electrical properties in Drosophila neurons developing without synaptic transmission. J Neurosci 21:1523–1531. Blichenberg A, Schwanke B, Rehbein M, Garner CC, Richter D, Kindler S (1999) Identification of a cis-acting dendritic targeting element in MAP2 mRNAs. J Neurosci 19:8818–8829. Broadie K, Prokop A, Bellen HJ, O’Kane CJ, Schulze KL, Sweeney ST (1995) Syntaxin and synaptobrevin function downstream of vesicle docking in Drosophila. Neuron 15:663–673. Burrone J, Murthy VK (2003) Synaptic gain control and homeostasis. Curr Opin Neurobiol 13:560–567. Burrone J, O’Byrne M, Murthy VN (2002) Multiple forms of synaptic plasticity triggered by selective suppression of activity in individual neurons. Nature 420:414–418. Cantrell AR, Catterall WA (2001) Neuromodulation of Na channels: an unexpected form of cellular plasticity. Nat Rev Neurosci 2:397–407. Catterall WA (2000) From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron 26:13–25. Chagnovich D, Lehmann R (2001) Poly(A)-independent regulation of maternal hunchback translation in the Drosophila embryo. Proc Natl Acad Sci USA 98:11359–11364. Davis GW, DiAntonio A, Petersen SA, Goodman CS (1998) Postsynaptic PKA controls quantal size and reveals a retrograde signal that regulates presynaptic transmitter release in Drosophila. Neuron 20:305–315. Davis RL, Cherry J, Dauwalder B, Han PL, Skoulakis E (1995) The cyclic AMP system and Drosophila learning. Mol Cell Biochem 149/150:271–278. Desai NS, Rutherford L, Turrigiano GG (1999) Plasticity in the intrinsic excitability of cortical pyramidal neurons. Nat Neurosci 2:515–520. Dubnau J, Chiang AS, Grady L, Barditch J, Gossweiler S, McNeil J, Smith P, Buldoc F, Scott R, Certa U, Broger C, Tully T (2003) The staufen/pumilio pathway is involved in Drosophila long-term memory. Curr Biol 13:286–296. Dudai Y, Jan YN, Byers D, Quinn WG, Benzer S (1976) dunce, a mutant of Drosophila deficient in learning. Proc Natl Acad Sci USA 73:1684–1688. Fujioka M, Emi-Sarker Y, Yusibova GL, Goto T, Jaynes JB (1999) Analysis of an even-skipped rescue transgene reveals both composite and discrete neuronal and early blastoderm enhancers, and multi-stripe positioning by gap gene repressor gradients. Development 126:2527–2538. Gavis ER (2001) Over the rainbow to translational control. Nat Struct Biol 8:387–389. Hicks GG, Singh N, Nashabi A, Mai S, Bozek G, Klewes L, Arapovic D, White EK, Kroury MJ, Oltz EM, Van Kaer L, Ruley HE (2000) Fus deficiency in mice results in defective B-lymphocyte development and activation, high levels of chromosomal instability and perinatal death. Nat Genet 24:175–179. Hong CS, Ganetzky B (1994) Spatial and temporal expression patterns of two sodium channel genes in Drosophila. J Neurosci 14:5160–5169. Leslie KR, Nelson SB, Turrigiano GG (2001) Postsynaptic depolarization scales quantal amplitude in cortical pyramidal neurons. J Neurosci 21:RC170(1–6). Li M, West JW, Lai Y, Scheuer T, Catterall WA (1992) Functional modulation of brain sodium channels by cAMP-dependent phosphorylation. Neuron 8:1151–1159. Li Y, Bennett DJ (2003) Persistent sodium and calcium currents cause plateau potentials in motoneurons of chronic spinal rats. J Neurophysiol 90:857–869. Li Y, Gorassini MA, Bennett DJ (2004) Role of persistent sodium and calcium currents in motoneuron firing and spasticity in chronic spinal rats. J Neurophysiol 91:767–783. MacLean JN, Zhang Y, Johnson BR, Harris-Warrick RM (2003) Activityindependent homeostasis in rhythmically active neurons. Neuron 37:109–120. Mantegazza M, Franceschetti S, Avanzini G (1998) Anemone toxin (ATX II)-induced increase in persistent sodium current: effects on the firing properties of rat neocortical pyramidal neurons. J Physiol (Lond) 507:105–116. O’Brien RJ, Kamboj S, Ehlers MD, Rosen KR, Fischbach GD, Huganir RL (1998) Activity-dependent modulation of synaptic AMPA receptor accumulation. Neuron 21:1067–1078. O’Dowd DK, Germeraad SE, Aldrich RW (1989) Alterations in the expression and gating of Drosophila sodium channels by mutations in the para gene. Neuron 2:1301–1311. O’Dowd DK, Gee JR, Smith MA (1995) Sodium current density correlates with expression of specific alternatively spliced sodium channel mRNAs in single neurons. J Neurosci 15:4005–4012. Paradis S, Sweeney ST, DavisGW (2001) Homeostatic control of presynaptic release is triggered by postsynaptic membrane depolarization. Neuron 30:737–749. Raman IM, Sprunger LK, Meisler MH, Bean BP (1997) Altered subthreshold sodium currents and disrupted firing patterns in Purkinje neurons of Scn8a mutant mice. Neuron 19:881–891. Rohrbough J, O’Dowd DK, Baines RA, Broadie K (2003) Cellular bases of behavioral plasticity: establishing and modifying synaptic circuits in the Drosophila genetic system. J Neurobiol 54:254–271. Schweers BA, Walters KJ, Stern M (2002) The Drosophila melanogaster translational repressor pumilio regulates neuronal excitability. Genetics 161:1177–1185. Smith RD, Goldin AL (1997) Phosphorylation at a single site in the rat brain sodium channel is necessary and sufficient for current reduction by protein kinase A. J Neurosci 17:6086–6093. Sonoda J, Wharton RP (1999) Recruitment of Nanos to hunchback mRNA by Pumilio. Genes Dev 13:2704–2712. Stern M, Kreber R, Ganetzky B (1990) Dosage effects of a Drosophila sodium channel gene on behavior and axonal excitability. Genetics 124:133–143. Sweeney ST, Broadie K, Keane J, Niemann H, O’Kane J (1995) Targeted expression of tetanus toxin light chain in Drosophila specifically eliminates synaptic transmission and causes behavioral defects. Neuron 14:341–351. Tautz D (1988) Regulation of Drosophila segmentation gene hunchback by two maternal morphogenetic centres. Nature 332:281–284. Thackeray JR, Ganetzky B (1994) Developmentally regulated alternative splicing generates a complex array of Drosophila para sodium channel isoforms. J Neurosci 14:2569–2578. Thackeray JR, Ganetzky B (1995) Conserved alternative splicing patterns and splicing signals in the Drosophila sodium channel gene para. Genetics 141:203–214. Turrigiano GG (1999) Homeostatic plasticity in neural networks: the more things change, the more they stay the same. Trends Neurosci 22:221–227. Turrigiano GG, Nelson SB (2000) Hebb and homeostasis in neuronal plasticity. Curr Opin Neurobiol 10:358–364. Turrigiano GG, Nelson SB (2004) Homeostatic plasticity in the developing nervous system. Nat Rev Neurosci 5:97–107. Turrigiano GG, Abbot LF, Marder E (1994) Activity-dependent changes in the intrinsic properties of cultured neurons. Science 264:974–977. Turrigiano GG, LeMasson G, Marder E (1995) Selective regulation of current densities underlies spontaneous changes in activity in cultured neurons. J Neurosci 15:3640–3652. Turrigiano GG, Leslie KR, Desai NS, Rutherford LC, Nelson SB (1998) Activity-dependent scaling of quantal amplitude in neocortical neurons. Nature 391:892–896. Walker J, Dale M, Standart N (1996) Unmasking mRNA in clam oocytes: role of phosphorylation of a 3 UTR masking element-binding protein at fertilization. Dev Biol 11:2510–2521. Wang W, Caldwell MC, Lin S, Furneaux H, Gorospe M (2000) HuR regulates cyclin A and cyclin B1 mRNA stability during cell proliferation. EMBO J 19:2340–2350. West AE, Griffith EC, Greenberg ME (2002) Regulation of transcription factors by neuronal activity. Nat Rev Neurosci 3:921–931. Wharton RP, Struhl G (1991) RNA regulatory elements mediate control of Drosophila body pattern by the posterior morphogen nanos. Cell 67:955–967. Wharton RP, Sonoda J, Lee T, Patterson M, Murata Y (1998) The Pumilio RNA-binding domain is also a translational repressor. Mol Cell 1:863–872. Wreden C, Verotti AC, Schisa JA, Lieberfarb ME, Strickland S (1997) Nanos and pumilio establish embryonic polarity in Drosophila by promoting posterior deadenylation of hunchback mRNA. Development 124:3015–3023. Ye B, Petritsch C, Clark IE, Gavis ER, Jan LY, Jan YN (2004) Nanos and Pumilio are essential for dendrite morphogenesis in Drosophila peripheral neurons. Curr Biol 14:314–321. Zamore PD, Williamson JR, Lehmann R (1997) The Pumilio protein binds RNA through a conserved domain that defines a new class of RNAbinding proteins. RNA 3:1421–1433. Zars T, Wolf R, Davis R, HeisenbergM (2000) Tissue-specific expression of a type I adenylyl cyclase rescues the rutabaga mutant memory defect: in search of the engram. Learn Mem 7:18–31. Zhang H, Tan J, Reynolds E, Kuebler D, Faulhaber S, TanouyeM (2002) The Drosophila slamdance gene: a mutation in an aminopeptidase can cause seizure, paralysis and neuronal failure. Genetics 162:1283–1299.
URI:	http://wrap.warwick.ac.uk/id/eprint/2558

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