Differential Effect of Alpha-latrotoxin on Exocytosis from Small Synaptic Vesicles and from Large Dense-core Vesicles Containing Calcitonin Gene-related Peptide at the Frog Neuromuscular Junction

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1988 Oct 1

PMID 3050995

Citations 49

Authors

M Matteoli

C Haimann

J M Polak

B Ceccarelli

P De Camilli

Affiliations

Soon will be listed here.

Abstract

The regulatory peptide called calcitonin gene-related peptide (CGRP) was detected by immunofluorescence in frog motor neurons and motor nerve terminals. In motor nerve terminals, CGRP-like immunoreactivity was found to be segregated within large dense-core vesicles. To determine whether exocytosis from acetylcholine-containing small synaptic vesicles and from CGRP-containing large dense-core vesicles can be independently stimulated, nerve-muscle preparations were exposed to alpha-latrotoxin. This toxin induced complete depletion of acetylcholine-containing small synaptic vesicles but did not induce a parallel depletion of CGRP-like immunoreactivity and of large dense-core vesicles. These effects were independent of the presence of extracellular Ca2+ and occurred both at room temperature and at low temperature (1-3 degrees C). These findings suggest that exocytosis from the two vesicle populations is mediated by distinct biochemical mechanisms, which might be differentially regulated by physiological stimuli.

Citing Articles

A comprehensive review on calcitonin gene-related peptide in the management of gastrointestinal disorders.

Sandu R, Singh J Inflammopharmacology. 2025; .

PMID: 39934537 DOI: 10.1007/s10787-025-01657-6.

The potential role of CGRP in synuclein-associated neurodegenerative disorders.

Alexoudi A, Donadio V, Karageorgiou E Front Neurosci. 2024; 18:1479830.

PMID: 39568667 PMC: 11576422. DOI: 10.3389/fnins.2024.1479830.

Neuro-bone tissue engineering: emerging mechanisms, potential strategies, and current challenges.

Sun W, Ye B, Chen S, Zeng L, Lu H, Wan Y Bone Res. 2023; 11(1):65.

PMID: 38123549 PMC: 10733346. DOI: 10.1038/s41413-023-00302-8.

Antinociceptive effect of the calcitonin gene-related peptide receptor antagonist BIBN4096BS in mice with bacterial cystitis.

Montalbetti N, Dalghi M, Parakala-Jain T, Clayton D, Apodaca G, Carattino M Am J Physiol Renal Physiol. 2023; 325(6):F779-F791.

PMID: 37823199 PMC: 10878727. DOI: 10.1152/ajprenal.00217.2023.

Calcitonin Gene-Related Peptide Systemic Effects: Embracing the Complexity of Its Biological Roles-A Narrative Review.

Bonura A, Brunelli N, Marcosano M, Iaccarino G, Fofi L, Vernieri F Int J Mol Sci. 2023; 24(18).

PMID: 37762283 PMC: 10530509. DOI: 10.3390/ijms241813979.

References

Edstrom A, Hanson M . Temperature effects on fast axonal transport of proteins in vitro in frog sciatic nerves. Brain Res. 1973; 58(2):345-54. DOI: 10.1016/0006-8993(73)90006-1. View

FRONTALI N, Ceccarelli B, Gorio A, Mauro A, Siekevitz P, Tzeng M . Purification from black widow spider venom of a protein factor causing the depletion of synaptic vesicles at neuromuscular junctions. J Cell Biol. 1976; 68(3):462-79. PMC: 2109651. DOI: 10.1083/jcb.68.3.462. View

Lynch K . Stimulation-induced reduction of large dense core vesicle numbers in cholinergic motor nerve endings. Brain Res. 1980; 194(1):249-54. DOI: 10.1016/0006-8993(80)91338-4. View

Ceccarelli B, HURLBUT W . Ca2+-dependent recycling of synaptic vesicles at the frog neuromuscular junction. J Cell Biol. 1980; 87(1):297-303. PMC: 2110728. DOI: 10.1083/jcb.87.1.297. View

Andersson P, Bloom S, Edwards A, Jarhult J . Effects of stimulation of the chorda tympani in bursts on submaxillary responses in the cat. J Physiol. 1982; 322:469-83. PMC: 1249683. DOI: 10.1113/jphysiol.1982.sp014050. View

Amara S, JONAS V, Rosenfeld M, Ong E, Evans R . Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products. Nature. 1982; 298(5871):240-4. DOI: 10.1038/298240a0. View

De Camilli P, Cameron R, Greengard P . Synapsin I (protein I), a nerve terminal-specific phosphoprotein. I. Its general distribution in synapses of the central and peripheral nervous system demonstrated by immunofluorescence in frozen and plastic sections. J Cell Biol. 1983; 96(5):1337-54. PMC: 2112636. DOI: 10.1083/jcb.96.5.1337. View

Rosenfeld M, Mermod J, Amara S, Swanson L, Sawchenko P, Rivier J . Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing. Nature. 1983; 304(5922):129-35. DOI: 10.1038/304129a0. View

Mason R, Peterfreund R, Sawchenko P, Corrigan A, Rivier J, Vale W . Release of the predicted calcitonin gene-related peptide from cultured rat trigeminal ganglion cells. Nature. 1984; 308(5960):653-5. DOI: 10.1038/308653a0. View

10.

Ip N, Zigmond R . Pattern of presynaptic nerve activity can determine the type of neurotransmitter regulating a postsynaptic event. Nature. 1984; 311(5985):472-4. DOI: 10.1038/311472a0. View

11.

Keller G, Tokuyasu K, Dutton A, Singer S . An improved procedure for immunoelectron microscopy: ultrathin plastic embedding of immunolabeled ultrathin frozen sections. Proc Natl Acad Sci U S A. 1984; 81(18):5744-7. PMC: 391787. DOI: 10.1073/pnas.81.18.5744. View

12.

Gibson S, Polak J, Bloom S, Sabate I, Mulderry P, Ghatei M . Calcitonin gene-related peptide immunoreactivity in the spinal cord of man and of eight other species. J Neurosci. 1984; 4(12):3101-11. PMC: 6564846. View

13.

Navone F, Greengard P, De Camilli P . Synapsin I in nerve terminals: selective association with small synaptic vesicles. Science. 1984; 226(4679):1209-11. DOI: 10.1126/science.6438799. View

14.

Segal J, Ceccarelli B, Fesce R, HURLBUT W . Miniature endplate potential frequency and amplitude determined by an extension of Campbell's theorem. Biophys J. 1985; 47(2 Pt 1):183-202. PMC: 1435151. DOI: 10.1016/s0006-3495(85)83891-1. View

15.

Rodrigo J, Polak J, Terenghi G, Cervantes C, Ghatei M, Mulderry P . Calcitonin gene-related peptide (CGRP)-immunoreactive sensory and motor nerves of the mammalian palate. Histochemistry. 1985; 82(1):67-74. DOI: 10.1007/BF00502092. View

16.

Mulderry P, Ghatei M, Rodrigo J, Allen J, Rosenfeld M, Polak J . Calcitonin gene-related peptide in cardiovascular tissues of the rat. Neuroscience. 1985; 14(3):947-54. DOI: 10.1016/0306-4522(85)90156-3. View

17.

Haimann C, Fesce R, Ceccarelli B . Measurement of quantal secretion induced by ouabain and its correlation with depletion of synaptic vesicles. J Cell Biol. 1985; 101(5 Pt 1):1953-65. PMC: 2113948. DOI: 10.1083/jcb.101.5.1953. View

18.

Takami K, Kawai Y, Uchida S, Tohyama M, Shiotani Y, Yoshida H . Effect of calcitonin gene-related peptide on contraction of striated muscle in the mouse. Neurosci Lett. 1985; 60(2):227-30. DOI: 10.1016/0304-3940(85)90248-4. View

19.

Wanke E, Ferroni A, Gattanini P, Meldolesi J . alpha Latrotoxin of the black widow spider venom opens a small, non-closing cation channel. Biochem Biophys Res Commun. 1986; 134(1):320-5. DOI: 10.1016/0006-291x(86)90565-6. View

20.

Fesce R, Segal J, Ceccarelli B, HURLBUT W . Effects of black widow spider venom and Ca2+ on quantal secretion at the frog neuromuscular junction. J Gen Physiol. 1986; 88(1):59-81. PMC: 2228788. DOI: 10.1085/jgp.88.1.59. View