Protein kinase C regulates local synthesis and secretion of a neuropeptide required for activity-dependent long-term synaptic plasticity.
Long-term facilitation (LTF) of sensory neuron synapses in Aplysia is produced by either nonassociative or associative stimuli. Nonassociative LTF can be produced by five spaced applications of serotonin (5-HT) and requires a phosphoinosotide 3-kinase (PI3K)-dependent and rapamycin-sensitive increase in the local synthesis of the sensory neuron neuropeptide sensorin and a protein kinase A (PKA)-dependent increase in the secretion of the newly synthesized sensorin. We report here that associative LTF produced by a single pairing of a brief tetanus with one application of 5-HT requires a rapid protein kinase C (PKC)-dependent and rapamycin-sensitive increase in local sensorin synthesis. This rapid increase in sensorin synthesis does not require PI3K activity or the presence of the sensory neuron cell body but does require the presence of the motor neuron. The secretion of newly synthesized sensorin by 2 h after stimulation requires both PKA and PKC activities to produce associative LTF because incubation with exogenous anti-sensorin antibody or the kinase inhibitors after tetanus plus 5-HT blocked LTF. The secreted sensorin leads to phosphorylation and translocation of p42/44 mitogen-activated protein kinase (MAPK) into the nuclei of the sensory neurons. Thus, different stimuli activating different signaling pathways converge by regulating the synthesis and release of a neuropeptide to produce long-term synaptic plasticity.
Hu
Jiang-Yuan
JY
Center for Neurobiology and Behavior, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, New York, New York 10032, USA.
Chen
Yang
Y
Schacher
Samuel
S
D000704:Analysis of Variance; D000818:Animals; D001048:Aplysia; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017952:Ganglia, Invertebrate; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009046:Motor Neurons / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D013569:Synapses / Q000502:physiology*
D004791:Enzyme Inhibitors; D009479:Neuropeptides; D012701:Serotonin; D011493:Protein Kinase C
J Neurosci. 1999 Aug 1;19(15):6338-47
10414963
Learn Mem. 1994 Sep-Oct;1(3):189-202
10467596
J Neurochem. 1999 Dec;73(6):2415-23
10582601
Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14577-82
10588747
Learn Mem. 1998 Mar-Apr;4(6):496-509
10701874
Nat Neurosci. 2000 Apr;3(4):323-9
10725920
Neuron. 2000 Apr;26(1):219-31
10798406
Nat Neurosci. 2000 Jun;3(6):533-5
10816306
Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11581-6
11027355
J Neurosci. 2001 Feb 15;21(4):1247-56
11160395
J Neurosci. 2001 Jan 15;21(2):382-91
11160419
Science. 2001 Nov 2;294(5544):1030-8
11691980
Nat Neurosci. 2002 Apr;5(4):295-6
11914719
J Neurosci. 2002 Apr 1;22(7):2669-78
11923432
J Neurosci. 2002 Jul 1;22(13):5412-22
12097493
J Biol Chem. 2002 Oct 4;277(40):37116-23
12140280
J Biol Chem. 2002 Oct 25;277(43):40633-9
12183453
J Neurosci. 2002 Nov 1;22(21):9278-86
12417653
Neuron. 2003 Feb 6;37(3):473-84
12575954
J Neurosci. 2003 Mar 1;23(5):1804-15
12629184
J Neurosci. 2003 Apr 1;23(7):2675-85
12684453
J Neurosci. 2003 Jul 16;23(15):6238-44
12867508
J Neurobiol. 2003 Sep 5;56(3):275-86
12884266
Neuron. 1992 May;8(5):883-9
1316764
Neuron. 1992 Oct;9(4):749-58
1356372
Neuron. 2003 Sep 25;40(1):151-65
14527440
Trends Neurosci. 2003 Dec;26(12):662-70
14624850
J Neurosci. 2004 Mar 10;24(10):2465-74
15014122
J Neurosci. 2004 Apr 7;24(14):3600-9
15071108
J Neurophysiol. 1992 Aug;68(2):643-51
1527580
Neuron. 2004 Aug 5;43(3):373-85
15294145
J Neurosci. 2004 Nov 3;24(44):9933-43
15525778
Neuron. 2004 Nov 18;44(4):715-28
15541318
Ageing Res Rev. 2004 Nov;3(4):407-30
15541709
J Neurosci. 1992 Apr;12(4):1160-8
1556591
J Neurosci. 2005 Feb 23;25(8):1979-84
15728837
Neuron. 2005 Mar 24;45(6):887-901
15797550
J Neurosci. 2006 Jan 18;26(3):1026-35
16421322
Neuron. 2006 Feb 2;49(3):349-56
16446139
Brain Res. 1991 Jan 25;539(2):324-7
1647242
J Neurosci. 1991 Sep;11(9):2655-65
1679120
J Neurosci. 2006 Aug 23;26(34):8847-56
16928874
Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14206-10
16963562
J Neurophysiol. 2007 Jan;97(1):134-43
16971689
J Neurosci. 1990 Oct;10(10):3286-94
1698945
Nat Neurosci. 2007 Jan;10(1):49-57
17128266
Learn Mem. 2007 Apr 02;14(4):236-46
17404386
J Neurosci. 1991 Aug;11(8):2303-13
1869917
Nature. 1990 Jun 21;345(6277):718-21
2141668
Proc Natl Acad Sci U S A. 1990 Mar;87(5):2036-9
2155431
Science. 1990 Jul 27;249(4967):420-3
2165631
Science. 1990 Aug 17;249(4970):799-802
2389145
Nature. 1989 May 4;339(6219):51-4
2469963
Nature. 1985 Jan 31-Feb 6;313(6001):392-5
2578623
J Neurosci. 1989 May;9(5):1774-80
2723749
Proc Natl Acad Sci U S A. 1985 Apr;82(8):2548-52
2986121
Nature. 1987 Sep 3-9;329(6134):62-5
3041225
Proc Natl Acad Sci U S A. 1988 Apr;85(7):2373-7
3353385
Science. 1986 Dec 5;234(4781):1249-54
3775383
J Neurosci. 1986 Mar;6(3):759-63
3958793
J Neurosci. 1982 Dec;2(12):1682-91
6292380
Science. 1983 Apr 1;220(4592):91-3
6828885
J Neurosci. 1995 Nov;15(11):7517-27
7472503
Science. 1993 Apr 9;260(5105):222-6
7682336
Neuron. 1993 Jun;10(6):1079-88
7686379
Proc Biol Sci. 1994 Mar 22;255(1344):215-21
7912832
Cell. 1994 Mar 25;76(6):1099-114
8137425
J Neurosci. 1994 Jan;14(1):368-83
8283244
Mol Cell Neurosci. 1996 Mar;7(3):222-38
8726105
J Neurophysiol. 1996 Oct;76(4):2250-61
8899600
J Neurosci. 1997 Jan 15;17(2):597-606
8987782
J Neurosci. 1997 Jul 1;17(13):4976-86
9185535
Neuron. 1997 Jun;18(6):899-912
9208858
Neuron. 1997 Jun;18(6):913-24
9208859
J Neurosci. 1997 Oct 1;17(19):7237-44
9295370
Science. 1997 Oct 17;278(5337):467-71
9334306
Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1864-9
9465108
J Neurosci. 1998 Jun 1;18(11):3991-4000
9592080
J Neurochem. 1998 Sep;71(3):1221-31
9721748
Cell. 1998 Oct 16;95(2):211-23
9790528
J Neurophysiol. 1998 Nov;80(5):2514-20
9819259
J Neurosci. 1999 Jan 15;19(2):589-98
9880579
Neuron. 1998 Dec;21(6):1423-34
9883734