Regulation of Neuroblast Mitosis is Determined by PACAP Receptor Isoform Expression

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2001 Apr 11

PMID 11296303

Citations 37

Authors

A Nicot

E DiCicco-Bloom

Affiliations

Soon will be listed here.

Abstract

Although neurogenesis in the embryo proceeds in a region- or lineage-specific fashion coincident with neuropeptide expression, a regulatory role for G protein-coupled receptors (GPCR) remains undefined. Pituitary adenylate cyclase activating polypeptide (PACAP) stimulates sympathetic neuroblast proliferation, whereas the peptide inhibits embryonic cortical precursor mitosis. Here, by using ectopic expression strategies, we show that the opposing mitogenic effects of PACAP are determined by expression of PACAP receptor splice isoforms and differential coupling to the phospholipase C (PLC) pathway, as opposed to differences in cellular context. In embryonic day 14 (E14) cortical precursors transfected with the hop receptor variant, but not cells transfected with the short variant, PACAP activates the PLC pathway, increasing intracellular calcium and eliciting translocation of protein kinase C. Ectopic expression of the hop variant in cortical neuroblasts transforms the antimitotic effect of PACAP into a promitogenic signal. Furthermore, PACAP promitogenic effects required PLC pathway function indicated by antagonist U-73122 studies in hop-transfected cortical cells and native sympathetic neuroblasts. These observations highlight the critical role of lineage-specific expression of GPCR variants in determining mitogenic signaling in neural precursors.

Citing Articles

Dysregulation of mTOR signaling mediates common neurite and migration defects in both idiopathic and 16p11.2 deletion autism neural precursor cells.

Prem S, Dev B, Peng C, Mehta M, Alibutud R, Connacher R Elife. 2024; 13.

PMID: 38525876 PMC: 11003747. DOI: 10.7554/eLife.82809.

Targeting VIP and PACAP Receptor Signaling: New Insights into Designing Drugs for the PACAP Subfamily of Receptors.

Lu J, Piper S, Zhao P, Miller L, Wootten D, Sexton P Int J Mol Sci. 2022; 23(15).

PMID: 35897648 PMC: 9331257. DOI: 10.3390/ijms23158069.

Activation of the VPAC2 Receptor Impairs Axon Outgrowth and Decreases Dendritic Arborization in Mouse Cortical Neurons by a PKA-Dependent Mechanism.

Takeuchi S, Kawanai T, Yamauchi R, Chen L, Miyaoka T, Yamada M Front Neurosci. 2020; 14:521.

PMID: 32581681 PMC: 7287155. DOI: 10.3389/fnins.2020.00521.

Splice-specific deficiency of the PTSD-associated gene PAC1 leads to a paradoxical age-dependent stress behavior.

Biran J, Gliksberg M, Shirat I, Swaminathan A, Levitas-Djerbi T, Appelbaum L Sci Rep. 2020; 10(1):9559.

PMID: 32533011 PMC: 7292827. DOI: 10.1038/s41598-020-66447-2.

Review on PACAP-Induced Transcriptomic and Proteomic Changes in Neuronal Development and Repair.

Rivnyak A, Kiss P, Tamas A, Balogh D, Reglodi D Int J Mol Sci. 2018; 19(4).

PMID: 29596316 PMC: 5979407. DOI: 10.3390/ijms19041020.

References

Lu N, DiCicco-Bloom E . Pituitary adenylate cyclase-activating polypeptide is an autocrine inhibitor of mitosis in cultured cortical precursor cells. Proc Natl Acad Sci U S A. 1997; 94(7):3357-62. PMC: 20374. DOI: 10.1073/pnas.94.7.3357. View

Basille M, Gonzalez B, Desrues L, Demas M, Fournier A, Vaudry H . Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates adenylyl cyclase and phospholipase C activity in rat cerebellar neuroblasts. J Neurochem. 1995; 65(3):1318-24. DOI: 10.1046/j.1471-4159.1995.65031318.x. View

Conchon S, Barrault M, Miserey S, Corvol P, Clauser E . The C-terminal third intracellular loop of the rat AT1A angiotensin receptor plays a key role in G protein coupling specificity and transduction of the mitogenic signal. J Biol Chem. 1997; 272(41):25566-72. DOI: 10.1074/jbc.272.41.25566. View

Sakai N, Sasaki K, Ikegaki N, Shirai Y, Ono Y, Saito N . Direct visualization of the translocation of the gamma-subspecies of protein kinase C in living cells using fusion proteins with green fluorescent protein. J Cell Biol. 1998; 139(6):1465-76. PMC: 2132627. DOI: 10.1083/jcb.139.6.1465. View

Vaudry D, Gonzalez B, Basille M, Anouar Y, Fournier A, Vaudry H . Pituitary adenylate cyclase-activating polypeptide stimulates both c-fos gene expression and cell survival in rat cerebellar granule neurons through activation of the protein kinase A pathway. Neuroscience. 1998; 84(3):801-12. DOI: 10.1016/s0306-4522(97)00545-9. View

Moroo I, Tatsuno I, Uchida D, Tanaka T, Saito J, Saito Y . Pituitary adenylate cyclase activating polypeptide (PACAP) stimulates mitogen-activated protein kinase (MAPK) in cultured rat astrocytes. Brain Res. 1998; 795(1-2):191-6. DOI: 10.1016/s0006-8993(98)00291-1. View

Harmar A, Arimura A, Gozes I, Journot L, Laburthe M, Pisegna J . International Union of Pharmacology. XVIII. Nomenclature of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. Pharmacol Rev. 1998; 50(2):265-70. PMC: 6721840. View

Waschek J, Casillas R, Nguyen T, CARPENTER E, Rodriguez W . Neural tube expression of pituitary adenylate cyclase-activating peptide (PACAP) and receptor: potential role in patterning and neurogenesis. Proc Natl Acad Sci U S A. 1998; 95(16):9602-7. PMC: 21385. DOI: 10.1073/pnas.95.16.9602. View

Cameron H, Hazel T, McKay R . Regulation of neurogenesis by growth factors and neurotransmitters. J Neurobiol. 1998; 36(2):287-306. View

10.

Hapner S, Boeshore K, Large T, Lefcort F . Neural differentiation promoted by truncated trkC receptors in collaboration with p75(NTR). Dev Biol. 1998; 201(1):90-100. DOI: 10.1006/dbio.1998.8970. View

11.

Lu N, Zhou R, DiCicco-Bloom E . Opposing mitogenic regulation by PACAP in sympathetic and cerebral cortical precursors correlates with differential expression of PACAP receptor (PAC1-R) isoforms. J Neurosci Res. 1998; 53(6):651-62. DOI: 10.1002/(SICI)1097-4547(19980915)53:6<651::AID-JNR3>3.0.CO;2-4. View

12.

Maric D, Maric I, Smith S, Serafini R, Hu Q, Barker J . Potentiometric study of resting potential, contributing K+ channels and the onset of Na+ channel excitability in embryonic rat cortical cells. Eur J Neurosci. 1998; 10(8):2532-46. DOI: 10.1046/j.1460-9568.1998.00284.x. View

13.

Vaccarino F, Schwartz M, Raballo R, Nilsen J, Rhee J, Zhou M . Changes in cerebral cortex size are governed by fibroblast growth factor during embryogenesis. Nat Neurosci. 1999; 2(3):246-53. DOI: 10.1038/6350. View

14.

Dajani O, Sandnes D, Melien O, Rezvani F, Nilssen L, Thoresen G . Role of diacylglycerol (DAG) in hormonal induction of S phase in hepatocytes: the DAG-dependent protein kinase C pathway is not activated by epidermal growth factor (EGF), but is involved in mediating the enhancement of responsiveness to EGF by.... J Cell Physiol. 1999; 180(2):203-14. DOI: 10.1002/(SICI)1097-4652(199908)180:2<203::AID-JCP8>3.0.CO;2-T. View

15.

Reznikov K, Hauser K, Nazarevskaja G, Trunova Y, Derjabin V, Bakalkin G . Opioids modulate cell division in the germinal zone of the late embryonic neocortex. Eur J Neurosci. 1999; 11(8):2711-9. DOI: 10.1046/j.1460-9568.1999.00680.x. View

16.

Grimaldi M, Cavallaro S . Functional and molecular diversity of PACAP/VIP receptors in cortical neurons and type I astrocytes. Eur J Neurosci. 1999; 11(8):2767-72. DOI: 10.1046/j.1460-9568.1999.00693.x. View

17.

Braas K, May V . Pituitary adenylate cyclase-activating polypeptides directly stimulate sympathetic neuron neuropeptide Y release through PAC(1) receptor isoform activation of specific intracellular signaling pathways. J Biol Chem. 1999; 274(39):27702-10. DOI: 10.1074/jbc.274.39.27702. View

18.

Chun J . Lysophospholipid receptors: implications for neural signaling. Crit Rev Neurobiol. 1999; 13(2):151-68. DOI: 10.1615/critrevneurobiol.v13.i2.20. View

19.

Zhang Y, Altshuller Y, Hammond S, Hayes F, Morris A, Frohman M . Loss of receptor regulation by a phospholipase D1 mutant unresponsive to protein kinase C. EMBO J. 1999; 18(22):6339-48. PMC: 1171697. DOI: 10.1093/emboj/18.22.6339. View

20.

Bohn L, Belcheva M, Coscia C . Mitogenic signaling via endogenous kappa-opioid receptors in C6 glioma cells: evidence for the involvement of protein kinase C and the mitogen-activated protein kinase signaling cascade. J Neurochem. 2000; 74(2):564-73. PMC: 2504523. DOI: 10.1046/j.1471-4159.2000.740564.x. View