UNC-31 (CAPS) is required for dense-core vesicle but not synaptic vesicle exocytosis in Caenorhabditis elegans

Sean Speese, Matt Petrie, Kim Schuske, Michael Ailion, Kyoungsook Ann, Kouichi Iwasaki, Erik M. Jorgensen, Thomas F J Martin

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

Previous studies indicated that CAPS (calcium-dependent activator protein for secretion) functions as an essential component for the Ca 2+-dependent exocytosis of dense-core vesicles in neuroendocrine cells. However, recent mouse knock-out studies suggested an alternative role in the vesicular uptake or storage of catecholamines. To genetically assess the functional role of CAPS, we characterized the sole Caenorhabditis elegans CAPS ortholog UNC-31 (uncoordinated family member) and determined its role in dense-core vesicle-mediated peptide secretion and in synaptic vesicle recycling. Novel assays for dense-core vesicle exocytosis were developed by expressing a prepro-atrial natriuretic factor-green fluorescent protein fusion protein in C. elegans. unc-31 mutants exhibited reduced peptide release in vivo and lacked evoked peptide release in cultured neurons. In contrast, cultured neurons from unc-31 mutants exhibited normal stimulated synaptic vesicle recycling measured by FM4-64 [N-(3-triethylammoniumpropyl)-4-(6-(4-diethylamino)phenyl) hexatrienyl)pyridinium dibromide] dye uptake. Conversely, UNC-13, which exhibits sequence homology to CAPS/UNC-31, was found to be essential for synaptic vesicle but not dense-core vesicle exocytosis. These findings indicate that CAPS/UNC-31 function is not restricted to catecholaminergic vesicles but is generally required for and specific to dense-core vesicle exocytosis. Our results suggest that CAPS/UNC-31 and UNC-13 serve parallel and dedicated roles in dense-core vesicle and synaptic vesicle exocytosis, respectively, in the C. elegans nervous system.

Original languageEnglish (US)
Pages (from-to)6150-6162
Number of pages13
JournalJournal of Neuroscience
Volume27
Issue number23
DOIs
StatePublished - Jun 6 2007
Externally publishedYes

Fingerprint

Synaptic Vesicles
Exocytosis
Caenorhabditis elegans
Secretory Vesicles
Calmodulin
Caenorhabditis elegans Proteins
Peptides
Neurons
Neuroendocrine Cells
Atrial Natriuretic Factor
Sequence Homology
Green Fluorescent Proteins
Knockout Mice
Nervous System
Catecholamines
Coloring Agents

Keywords

  • C. elegans
  • CAPS
  • Dense-core vesicle
  • Exocytosis
  • Synaptic vesicle
  • UNC-13

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

UNC-31 (CAPS) is required for dense-core vesicle but not synaptic vesicle exocytosis in Caenorhabditis elegans. / Speese, Sean; Petrie, Matt; Schuske, Kim; Ailion, Michael; Ann, Kyoungsook; Iwasaki, Kouichi; Jorgensen, Erik M.; Martin, Thomas F J.

In: Journal of Neuroscience, Vol. 27, No. 23, 06.06.2007, p. 6150-6162.

Research output: Contribution to journalArticle

Speese, S, Petrie, M, Schuske, K, Ailion, M, Ann, K, Iwasaki, K, Jorgensen, EM & Martin, TFJ 2007, 'UNC-31 (CAPS) is required for dense-core vesicle but not synaptic vesicle exocytosis in Caenorhabditis elegans', Journal of Neuroscience, vol. 27, no. 23, pp. 6150-6162. https://doi.org/10.1523/JNEUROSCI.1466-07.2007
Speese, Sean ; Petrie, Matt ; Schuske, Kim ; Ailion, Michael ; Ann, Kyoungsook ; Iwasaki, Kouichi ; Jorgensen, Erik M. ; Martin, Thomas F J. / UNC-31 (CAPS) is required for dense-core vesicle but not synaptic vesicle exocytosis in Caenorhabditis elegans. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 23. pp. 6150-6162.
@article{d96456ceee6e4bfa84ef66cdbd7479a2,
title = "UNC-31 (CAPS) is required for dense-core vesicle but not synaptic vesicle exocytosis in Caenorhabditis elegans",
abstract = "Previous studies indicated that CAPS (calcium-dependent activator protein for secretion) functions as an essential component for the Ca 2+-dependent exocytosis of dense-core vesicles in neuroendocrine cells. However, recent mouse knock-out studies suggested an alternative role in the vesicular uptake or storage of catecholamines. To genetically assess the functional role of CAPS, we characterized the sole Caenorhabditis elegans CAPS ortholog UNC-31 (uncoordinated family member) and determined its role in dense-core vesicle-mediated peptide secretion and in synaptic vesicle recycling. Novel assays for dense-core vesicle exocytosis were developed by expressing a prepro-atrial natriuretic factor-green fluorescent protein fusion protein in C. elegans. unc-31 mutants exhibited reduced peptide release in vivo and lacked evoked peptide release in cultured neurons. In contrast, cultured neurons from unc-31 mutants exhibited normal stimulated synaptic vesicle recycling measured by FM4-64 [N-(3-triethylammoniumpropyl)-4-(6-(4-diethylamino)phenyl) hexatrienyl)pyridinium dibromide] dye uptake. Conversely, UNC-13, which exhibits sequence homology to CAPS/UNC-31, was found to be essential for synaptic vesicle but not dense-core vesicle exocytosis. These findings indicate that CAPS/UNC-31 function is not restricted to catecholaminergic vesicles but is generally required for and specific to dense-core vesicle exocytosis. Our results suggest that CAPS/UNC-31 and UNC-13 serve parallel and dedicated roles in dense-core vesicle and synaptic vesicle exocytosis, respectively, in the C. elegans nervous system.",
keywords = "C. elegans, CAPS, Dense-core vesicle, Exocytosis, Synaptic vesicle, UNC-13",
author = "Sean Speese and Matt Petrie and Kim Schuske and Michael Ailion and Kyoungsook Ann and Kouichi Iwasaki and Jorgensen, {Erik M.} and Martin, {Thomas F J}",
year = "2007",
month = "6",
day = "6",
doi = "10.1523/JNEUROSCI.1466-07.2007",
language = "English (US)",
volume = "27",
pages = "6150--6162",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "23",

}

TY - JOUR

T1 - UNC-31 (CAPS) is required for dense-core vesicle but not synaptic vesicle exocytosis in Caenorhabditis elegans

AU - Speese, Sean

AU - Petrie, Matt

AU - Schuske, Kim

AU - Ailion, Michael

AU - Ann, Kyoungsook

AU - Iwasaki, Kouichi

AU - Jorgensen, Erik M.

AU - Martin, Thomas F J

PY - 2007/6/6

Y1 - 2007/6/6

N2 - Previous studies indicated that CAPS (calcium-dependent activator protein for secretion) functions as an essential component for the Ca 2+-dependent exocytosis of dense-core vesicles in neuroendocrine cells. However, recent mouse knock-out studies suggested an alternative role in the vesicular uptake or storage of catecholamines. To genetically assess the functional role of CAPS, we characterized the sole Caenorhabditis elegans CAPS ortholog UNC-31 (uncoordinated family member) and determined its role in dense-core vesicle-mediated peptide secretion and in synaptic vesicle recycling. Novel assays for dense-core vesicle exocytosis were developed by expressing a prepro-atrial natriuretic factor-green fluorescent protein fusion protein in C. elegans. unc-31 mutants exhibited reduced peptide release in vivo and lacked evoked peptide release in cultured neurons. In contrast, cultured neurons from unc-31 mutants exhibited normal stimulated synaptic vesicle recycling measured by FM4-64 [N-(3-triethylammoniumpropyl)-4-(6-(4-diethylamino)phenyl) hexatrienyl)pyridinium dibromide] dye uptake. Conversely, UNC-13, which exhibits sequence homology to CAPS/UNC-31, was found to be essential for synaptic vesicle but not dense-core vesicle exocytosis. These findings indicate that CAPS/UNC-31 function is not restricted to catecholaminergic vesicles but is generally required for and specific to dense-core vesicle exocytosis. Our results suggest that CAPS/UNC-31 and UNC-13 serve parallel and dedicated roles in dense-core vesicle and synaptic vesicle exocytosis, respectively, in the C. elegans nervous system.

AB - Previous studies indicated that CAPS (calcium-dependent activator protein for secretion) functions as an essential component for the Ca 2+-dependent exocytosis of dense-core vesicles in neuroendocrine cells. However, recent mouse knock-out studies suggested an alternative role in the vesicular uptake or storage of catecholamines. To genetically assess the functional role of CAPS, we characterized the sole Caenorhabditis elegans CAPS ortholog UNC-31 (uncoordinated family member) and determined its role in dense-core vesicle-mediated peptide secretion and in synaptic vesicle recycling. Novel assays for dense-core vesicle exocytosis were developed by expressing a prepro-atrial natriuretic factor-green fluorescent protein fusion protein in C. elegans. unc-31 mutants exhibited reduced peptide release in vivo and lacked evoked peptide release in cultured neurons. In contrast, cultured neurons from unc-31 mutants exhibited normal stimulated synaptic vesicle recycling measured by FM4-64 [N-(3-triethylammoniumpropyl)-4-(6-(4-diethylamino)phenyl) hexatrienyl)pyridinium dibromide] dye uptake. Conversely, UNC-13, which exhibits sequence homology to CAPS/UNC-31, was found to be essential for synaptic vesicle but not dense-core vesicle exocytosis. These findings indicate that CAPS/UNC-31 function is not restricted to catecholaminergic vesicles but is generally required for and specific to dense-core vesicle exocytosis. Our results suggest that CAPS/UNC-31 and UNC-13 serve parallel and dedicated roles in dense-core vesicle and synaptic vesicle exocytosis, respectively, in the C. elegans nervous system.

KW - C. elegans

KW - CAPS

KW - Dense-core vesicle

KW - Exocytosis

KW - Synaptic vesicle

KW - UNC-13

UR - http://www.scopus.com/inward/record.url?scp=34250020729&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250020729&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.1466-07.2007

DO - 10.1523/JNEUROSCI.1466-07.2007

M3 - Article

C2 - 17553987

AN - SCOPUS:34250020729

VL - 27

SP - 6150

EP - 6162

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 23

ER -