A Neuropeptide Signaling Pathway Regulates Synaptic Growth in Drosophila

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2012 Feb 15

PMID 22331845

Citations 33

Authors

Xu Chen

Barry Ganetzky

Affiliations

Soon will be listed here.

Abstract

Neuropeptide signaling is integral to many aspects of neural communication, particularly modulation of membrane excitability and synaptic transmission. However, neuropeptides have not been clearly implicated in synaptic growth and development. Here, we demonstrate that cholecystokinin-like receptor (CCKLR) and drosulfakinin (DSK), its predicted ligand, are strong positive growth regulators of the Drosophila melanogaster larval neuromuscular junction (NMJ). Mutations of CCKLR or dsk produced severe NMJ undergrowth, whereas overexpression of CCKLR caused overgrowth. Presynaptic expression of CCKLR was necessary and sufficient for regulating NMJ growth. CCKLR and dsk mutants also reduced synaptic function in parallel with decreased NMJ size. Analysis of double mutants revealed that DSK/CCKLR regulation of NMJ growth occurs through the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element binding protein (CREB) pathway. Our results demonstrate a novel role for neuropeptide signaling in synaptic development. Moreover, because the cAMP-PKA-CREB pathway is required for structural synaptic plasticity in learning and memory, DSK/CCKLR signaling may also contribute to these mechanisms.

Citing Articles

The neuropeptide drosulfakinin enhances choosiness and protects males from the aging effects of social perception.

Fedina T, Cummins E, Promislow D, Pletcher S Proc Natl Acad Sci U S A. 2023; 120(51):e2308305120.

PMID: 38079545 PMC: 10743377. DOI: 10.1073/pnas.2308305120.

Effects of exercise-targeted hippocampal PDE-4 methylation on synaptic plasticity and spatial learning/memory impairments in D-galactose-induced aging rats.

Jin Y, Li X, Wei C, Yuan Q Exp Brain Res. 2023; 242(2):309-320.

PMID: 38052997 PMC: 10805951. DOI: 10.1007/s00221-023-06749-9.

A descending inhibitory mechanism of nociception mediated by an evolutionarily conserved neuropeptide system in .

Oikawa I, Kondo S, Hashimoto K, Yoshida A, Hamajima M, Tanimoto H Elife. 2023; 12.

PMID: 37310871 PMC: 10328526. DOI: 10.7554/eLife.85760.

Identification and functional characterization of the sulfakinin and sulfakinin receptor in the Chinese white pine beetle .

Liu B, Fu D, Ning H, Tang M, Chen H Front Physiol. 2022; 13:927890.

PMID: 36035480 PMC: 9417412. DOI: 10.3389/fphys.2022.927890.

Endocrine cybernetics: neuropeptides as molecular switches in behavioural decisions.

Nassel D, Zandawala M Open Biol. 2022; 12(7):220174.

PMID: 35892199 PMC: 9326288. DOI: 10.1098/rsob.220174.

References

DAVIS G, Schuster C, Goodman C . Genetic analysis of the mechanisms controlling target selection: target-derived Fasciclin II regulates the pattern of synapse formation. Neuron. 1997; 19(3):561-73. DOI: 10.1016/s0896-6273(00)80372-4. View

Rathmayer W, Djokaj S, Gaydukov A, Kreissl S . The neuromuscular junctions of the slow and the fast excitatory axon in the closer of the crab Eriphia spinifrons are endowed with different Ca2+ channel types and allow neuron-specific modulation of transmitter release by two neuropeptides. J Neurosci. 2002; 22(3):708-17. PMC: 6758538. View

Wolfgang W, Clay C, Parker J, Delgado R, Labarca P, Kidokoro Y . Signaling through Gs alpha is required for the growth and function of neuromuscular synapses in Drosophila. Dev Biol. 2004; 268(2):295-311. DOI: 10.1016/j.ydbio.2004.01.007. View

Collins C, Wairkar Y, Johnson S, DiAntonio A . Highwire restrains synaptic growth by attenuating a MAP kinase signal. Neuron. 2006; 51(1):57-69. DOI: 10.1016/j.neuron.2006.05.026. View

Nichols R . Signaling pathways and physiological functions of Drosophila melanogaster FMRFamide-related peptides. Annu Rev Entomol. 2002; 48:485-503. DOI: 10.1146/annurev.ento.48.091801.112525. View

Robb , Evans . THE MODULATORY EFFECT OF SCHISTOFLRFamide ON HEART AND SKELETAL MUSCLE IN THE LOCUST SCHISTOCERCA GREGARIA. J Exp Biol. 1994; 197(1):437-42. DOI: 10.1242/jeb.197.1.437. View

Stewart B, Atwood H, Renger J, Wang J, Wu C . Improved stability of Drosophila larval neuromuscular preparations in haemolymph-like physiological solutions. J Comp Physiol A. 1994; 175(2):179-91. DOI: 10.1007/BF00215114. View

Schmidt H, Stonkute A, Juttner R, Koesling D, Friebe A, Rathjen F . C-type natriuretic peptide (CNP) is a bifurcation factor for sensory neurons. Proc Natl Acad Sci U S A. 2009; 106(39):16847-52. PMC: 2757798. DOI: 10.1073/pnas.0906571106. View

Neves S, Ram P, Iyengar R . G protein pathways. Science. 2002; 296(5573):1636-9. DOI: 10.1126/science.1071550. View

10.

Featherstone D, Broadie K . Surprises from Drosophila: genetic mechanisms of synaptic development and plasticity. Brain Res Bull. 2001; 53(5):501-11. DOI: 10.1016/s0361-9230(00)00383-x. View

11.

Schuster C, DAVIS G, Fetter R, Goodman C . Genetic dissection of structural and functional components of synaptic plasticity. II. Fasciclin II controls presynaptic structural plasticity. Neuron. 1996; 17(4):655-67. DOI: 10.1016/s0896-6273(00)80198-1. View

12.

Koon A, Ashley J, Barria R, Dasgupta S, Brain R, Waddell S . Autoregulatory and paracrine control of synaptic and behavioral plasticity by octopaminergic signaling. Nat Neurosci. 2010; 14(2):190-9. PMC: 3391700. DOI: 10.1038/nn.2716. View

13.

Martin A . A further study of the statistical composition on the end-plate potential. J Physiol. 1955; 130(1):114-22. PMC: 1363457. DOI: 10.1113/jphysiol.1955.sp005397. View

14.

Nichols R . FMRFamide-related peptides and serotonin regulate Drosophila melanogaster heart rate: mechanisms and structure requirements. Peptides. 2006; 27(5):1130-7. DOI: 10.1016/j.peptides.2005.07.032. View

15.

Adams M, OShea M . Peptide cotransmitter at a neuromuscular junction. Science. 1983; 221(4607):286-9. DOI: 10.1126/science.6134339. View

16.

Nassel D . Neuropeptides in the nervous system of Drosophila and other insects: multiple roles as neuromodulators and neurohormones. Prog Neurobiol. 2002; 68(1):1-84. DOI: 10.1016/s0301-0082(02)00057-6. View

17.

Nichols R . Isolation and expression of the Drosophila drosulfakinin neural peptide gene product, DSK-I. Mol Cell Neurosci. 2009; 3(4):342-7. DOI: 10.1016/1044-7431(92)90031-v. View

18.

Manseau L, Baradaran A, Brower D, Budhu A, Elefant F, Phan H . GAL4 enhancer traps expressed in the embryo, larval brain, imaginal discs, and ovary of Drosophila. Dev Dyn. 1997; 209(3):310-22. DOI: 10.1002/(SICI)1097-0177(199707)209:3<310::AID-AJA6>3.0.CO;2-L. View

19.

McCudden C, Hains M, Kimple R, Siderovski D, Willard F . G-protein signaling: back to the future. Cell Mol Life Sci. 2005; 62(5):551-77. PMC: 2794341. DOI: 10.1007/s00018-004-4462-3. View

20.

Tettamanti M, Armstrong J, Endo K, Yang M, Furukubo-Tokunaga K, Kaiser K . Early development of the Drosophila mushroom bodies, brain centres for associative learning and memory. Dev Genes Evol. 2016; 207(4):242-252. DOI: 10.1007/s004270050112. View