Short- and long-term memory are modulated by multiple isoforms of the fragile X mental retardation protein.
The diversity of protein isoforms arising from alternative splicing is thought to modulate fine-tuning of synaptic plasticity. Fragile X mental retardation protein (FMRP), a neuronal RNA binding protein, exists in isoforms as a result of alternative splicing, but the contribution of these isoforms to neural plasticity are not well understood. We show that two isoforms of Drosophila melanogaster FMRP (dFMR1) have differential roles in mediating neural development and behavior functions conferred by the dfmr1 gene. These isoforms differ in the presence of a protein interaction module that is related to prion domains and is functionally conserved between FMRPs. Expression of both isoforms is necessary for optimal performance in tests of short- and long-term memory of courtship training. The presence or absence of the protein interaction domain may govern the types of ribonucleoprotein (RNP) complexes dFMR1 assembles into, with different RNPs regulating gene expression in a manner necessary for establishing distinct phases of memory formation.
Banerjee
Paromita
P
Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
Schoenfeld
Brian P
BP
Bell
Aaron J
AJ
Choi
Catherine H
CH
Bradley
Michael P
MP
Hinchey
Paul
P
Kollaros
Maria
M
Park
Jae H
JH
McBride
Sean M J
SM
Dockendorff
Thomas C
TC
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D002940:Circadian Rhythm / Q000502:physiology; D004252:DNA Mutational Analysis; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000502:physiology*; D008570:Memory, Short-Term / Q000502:physiology*; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000502:physiology; D009483:Neuropsychological Tests; D020033:Protein Isoforms / Q000378:metabolism; D012726:Sexual Behavior, Animal / Q000502:physiology; D013997:Time Factors
D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D020033:Protein Isoforms; C467328:FMR1 protein, Drosophila
Mol Neurobiol. 2009 Apr;39(2):107-29
19214804
J Neurosci. 2007 Dec 26;27(52):14349-57
18160642
Annu Rev Genet. 2000;34:205-232
11092827
J Neurosci. 2004 Jun 23;24(25):5798-809
15215302
J Neurosci. 2007 Mar 21;27(12):3120-30
17376973
Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9602-7
12871996
EMBO J. 1995 Jun 1;14(11):2401-8
7781595
Proc Natl Acad Sci U S A. 1997 May 13;94(10):5395-400
9144248
Hum Mol Genet. 1996 Jan;5(1):95-102
8789445
Nat Rev Genet. 2005 Jun;6(6):435-50
15931169
Proc Natl Acad Sci U S A. 2002 May 28;99(11):7746-50
12032354
Nat Genet. 2008 Dec;40(12):1413-5
18978789
Hum Mol Genet. 1993 Apr;2(4):399-404
8504300
Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4297-302
17360518
Hum Mol Genet. 1993 Aug;2(8):1147-53
8401496
Hum Mol Genet. 2009 Sep 1;18(17):3164-77
19487368
Am J Hum Genet. 2008 Jul;83(1):43-52
18589395
J Cell Biol. 2007 Nov 5;179(3):437-49
17984320
Mol Cell Biol. 2008 Feb;28(3):913-25
18070925
Nat Neurosci. 2007 Dec;10(12):1587-93
17965711
Neuron. 2007 Dec 20;56(6):955-62
18093519
Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8844-9
11438699
Mol Cell Biol. 2000 Nov;20(22):8536-47
11046149
Neuron. 2009 Jan 15;61(1):10-26
19146809
Cell. 2001 Nov 30;107(5):591-603
11733059
Neuron. 2006 Oct 5;52(1):93-101
17015229
Neuron. 2004 Sep 30;44(1):49-57
15450159
Neuron. 2003 Oct 30;40(3):581-94
14642281
Curr Opin Neurobiol. 2005 Jun;15(3):358-63
15961039
Nucleic Acids Res. 2008 Sep;36(15):4902-12
18653529
Trends Biochem Sci. 2007 Jun;32(6):279-85
17481902
Science. 2000 Jan 28;287(5453):661-4
10650001
Nucleic Acids Res. 1992 Mar 25;20(6):1425
1561104
Neuron. 2002 Jun 13;34(6):973-84
12086644
J Exp Biol. 2009 Aug;212(Pt 16):2564-70
19648401
Neuron. 2008 Oct 23;60(2):201-14
18957214
Genetics. 2007 Jul;176(3):1557-65
17507672
Genetics. 2007 Mar;175(3):1241-50
17194772
Development. 2003 Nov;130(22):5543-52
14530299
Nat Rev Neurosci. 2002 Oct;3(10):813-20
12360325
Science. 2000 May 19;288(5469):1254-7
10818003
Neuron. 2004 Sep 30;44(1):59-73
15450160
EMBO J. 1995 Nov 1;14(21):5358-66
7489725
J Mol Biol. 2004 Oct 8;343(1):43-53
15381419
Cell. 2009 Apr 3;137(1):146-58
19345193
Neuron. 2007 Apr 19;54(2):186-9
17442240
Cell. 2007 Apr 6;129(1):195-206
17418795
Nat Rev Microbiol. 2007 Aug;5(8):611-8
17632572
Science. 1988 Aug 19;241(4868):965-7
3043665
Curr Opin Neurobiol. 2004 Dec;14(6):745-50
15582378
Nat Genet. 1993 Jul;4(3):244-51
8358432
Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):11910-5
11050225
Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15281-6
18829439
Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5355-8
8202492
Mol Cell. 2000 Jan;5(1):163-72
10678178
Learn Mem. 2008 Jun 26;15(7):460-7
18583646
Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16859-64
16275927
J Neurophysiol. 2009 May;101(5):2572-80
19244359
Genetics. 2006 Nov;174(3):1287-98
16888325
Neuron. 2002 Jun 13;34(6):961-72
12086643
RNA. 2006 Aug;12(8):1446-9
16790844
Dev Cell. 2008 Jun;14(6):926-39
18539120
Genome Biol. 2003;4(6):R40
12801414
Learn Mem. 1999 Jan-Feb;6(1):1-20
10355520
Neuron. 2006 Aug 17;51(4):441-54
16908410
Neuron. 2005 Mar 3;45(5):753-64
15748850
Neuron. 1999 Dec;24(4):967-77
10624959
Neurobiol Dis. 2009 Jul;35(1):52-62
19362146
Nat Neurosci. 2008 Oct;11(10):1143-5
18776892
Proc Natl Acad Sci U S A. 1979 Jul;76(7):3430-4
16592682
Neuron. 2008 Sep 25;59(6):1024-36
18817739
Cell. 2003 Dec 26;115(7):879-91
14697205
Cell. 2010 Feb 5;140(3):421-35
20144764
Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18160-5
17110444