Genetic Analysis in Drosophila Reveals a Role for the Mitochondrial Protein P32 in Synaptic Transmission

Overview

Journal G3 (Bethesda)

Publisher Oxford University Press

Specialties Genetics
Molecular Biology

Date 2012 Mar 3

PMID 22384382

Citations 18

Authors

Andrew Lutas

Christopher J Wahlmark

Shaona Acharjee

Fumiko Kawasaki

Affiliations

Soon will be listed here.

Abstract

Mitochondria located within neuronal presynaptic terminals have been shown to play important roles in the release of chemical neurotransmitters. In the present study, a genetic screen for synaptic transmission mutants of Drosophila has identified the first mutation in a Drosophila homolog of the mitochondrial protein P32. Although P32 is highly conserved and has been studied extensively, its physiological role in mitochondria remains unknown and it has not previously been implicated in neural function. The Drosophila P32 mutant, referred to as dp32(EC1), exhibited a temperature-sensitive (TS) paralytic behavioral phenotype. Moreover, electrophysiological analysis at adult neuromuscular synapses revealed a TS reduction in the amplitude of excitatory postsynaptic currents (EPSC) and indicated that dP32 functions in neurotransmitter release. These studies are the first to address P32 function in Drosophila and expand our knowledge of mitochondrial proteins contributing to synaptic transmission.

Citing Articles

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References

Mattson M, Gleichmann M, Cheng A . Mitochondria in neuroplasticity and neurological disorders. Neuron. 2008; 60(5):748-66. PMC: 2692277. DOI: 10.1016/j.neuron.2008.10.010. View

Danjo R, Kawasaki F, Ordway R . A tripartite synapse model in Drosophila. PLoS One. 2011; 6(2):e17131. PMC: 3040228. DOI: 10.1371/journal.pone.0017131. View

Tang Y, Zucker R . Mitochondrial involvement in post-tetanic potentiation of synaptic transmission. Neuron. 1997; 18(3):483-91. DOI: 10.1016/s0896-6273(00)81248-9. View

Yu L, Zhang Z, Loewenstein P, Desai K, Tang Q, Mao D . Molecular cloning and characterization of a cellular protein that interacts with the human immunodeficiency virus type 1 Tat transactivator and encodes a strong transcriptional activation domain. J Virol. 1995; 69(5):3007-16. PMC: 189000. DOI: 10.1128/JVI.69.5.3007-3016.1995. View

Seytter T, Lottspeich F, Neupert W, Schwarz E . Mam33p, an oligomeric, acidic protein in the mitochondrial matrix of Saccharomyces cerevisiae is related to the human complement receptor gC1q-R. Yeast. 1998; 14(4):303-10. DOI: 10.1002/(SICI)1097-0061(19980315)14:4<303::AID-YEA217>3.0.CO;2-N. View

Dellinger B, Felling R, Ordway R . Genetic modifiers of the Drosophila NSF mutant, comatose, include a temperature-sensitive paralytic allele of the calcium channel alpha1-subunit gene, cacophony. Genetics. 2000; 155(1):203-11. PMC: 1461054. DOI: 10.1093/genetics/155.1.203. View

Twig G, Graf S, Wikstrom J, Mohamed H, Haigh S, Elorza A . Tagging and tracking individual networks within a complex mitochondrial web with photoactivatable GFP. Am J Physiol Cell Physiol. 2006; 291(1):C176-84. DOI: 10.1152/ajpcell.00348.2005. View

David G, Barrett E . Mitochondrial Ca2+ uptake prevents desynchronization of quantal release and minimizes depletion during repetitive stimulation of mouse motor nerve terminals. J Physiol. 2003; 548(Pt 2):425-38. PMC: 2342850. DOI: 10.1113/jphysiol.2002.035196. View

Verstreken P, Ly C, Venken K, Koh T, Zhou Y, Bellen H . Synaptic mitochondria are critical for mobilization of reserve pool vesicles at Drosophila neuromuscular junctions. Neuron. 2005; 47(3):365-78. DOI: 10.1016/j.neuron.2005.06.018. View

10.

Bruni R, Roizman B . Open reading frame P--a herpes simplex virus gene repressed during productive infection encodes a protein that binds a splicing factor and reduces synthesis of viral proteins made from spliced mRNA. Proc Natl Acad Sci U S A. 1996; 93(19):10423-7. PMC: 38400. DOI: 10.1073/pnas.93.19.10423. View

11.

Liu W, Gnanasambandam R, Benjamin J, Kaur G, Getman P, Siegel A . Mutations in cytochrome c oxidase subunit VIa cause neurodegeneration and motor dysfunction in Drosophila. Genetics. 2007; 176(2):937-46. PMC: 1894620. DOI: 10.1534/genetics.107.071688. View

12.

Muta T, Kang D, Kitajima S, Fujiwara T, Hamasaki N . p32 protein, a splicing factor 2-associated protein, is localized in mitochondrial matrix and is functionally important in maintaining oxidative phosphorylation. J Biol Chem. 1997; 272(39):24363-70. DOI: 10.1074/jbc.272.39.24363. View

13.

Honore B, Madsen P, Rasmussen H, Vandekerckhove J, Celis J, Leffers H . Cloning and expression of a cDNA covering the complete coding region of the P32 subunit of human pre-mRNA splicing factor SF2. Gene. 1993; 134(2):283-7. DOI: 10.1016/0378-1119(93)90108-f. View

14.

Vos M, Lauwers E, Verstreken P . Synaptic mitochondria in synaptic transmission and organization of vesicle pools in health and disease. Front Synaptic Neurosci. 2011; 2:139. PMC: 3059669. DOI: 10.3389/fnsyn.2010.00139. View

15.

Ghebrehiwet B, Lim B, Kumar R, Feng X, Peerschke E . gC1q-R/p33, a member of a new class of multifunctional and multicompartmental cellular proteins, is involved in inflammation and infection. Immunol Rev. 2001; 180:65-77. DOI: 10.1034/j.1600-065x.2001.1800106.x. View

16.

Rizvi F, Heimann T, Herrnreiter A, OBrien W . Mitochondrial dysfunction links ceramide activated HRK expression and cell death. PLoS One. 2011; 6(3):e18137. PMC: 3069046. DOI: 10.1371/journal.pone.0018137. View

17.

Krainer A, Mayeda A, Kozak D, Binns G . Functional expression of cloned human splicing factor SF2: homology to RNA-binding proteins, U1 70K, and Drosophila splicing regulators. Cell. 1991; 66(2):383-94. DOI: 10.1016/0092-8674(91)90627-b. View

18.

Tian L, Hires S, Mao T, Huber D, Chiappe M, Chalasani S . Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators. Nat Methods. 2009; 6(12):875-81. PMC: 2858873. DOI: 10.1038/nmeth.1398. View

19.

Rezin G, Amboni G, Zugno A, Quevedo J, Streck E . Mitochondrial dysfunction and psychiatric disorders. Neurochem Res. 2008; 34(6):1021-9. DOI: 10.1007/s11064-008-9865-8. View

20.

Kawasaki F, Iyer J, Posey L, Sun C, Mammen S, Yan H . The DISABLED protein functions in CLATHRIN-mediated synaptic vesicle endocytosis and exoendocytic coupling at the active zone. Proc Natl Acad Sci U S A. 2011; 108(25):E222-9. PMC: 3121831. DOI: 10.1073/pnas.1102231108. View