scholarly journals Dense core secretory vesicles revealed as a dynamic Ca2+store in neuroendocrine cells with a vesicle-associated membrane protein aequorin chimaera

2001 ◽  
Vol 155 (1) ◽  
pp. 41-52 ◽  
Author(s):  
Kathryn J. Mitchell ◽  
Paolo Pinton ◽  
Aniko Varadi ◽  
Carlo Tacchetti ◽  
Edward K. Ainscow ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Neuroendocrine Cells ◽  
Dense Core ◽  
Secretory Vesicles

scholarly journals HID-1 controls formation of large dense core vesicles by influencing cargo sorting and trans-Golgi network acidification

2017 ◽  
Vol 28 (26) ◽  
pp. 3870-3880 ◽  
Author(s):  
Blake H. Hummer ◽  
Noah F. de Leeuw ◽  
Christian Burns ◽  
Lan Chen ◽  
Matthew S. Joens ◽  
...  
Keyword(s):  
Biochemical Properties ◽  
Neuroendocrine Cells ◽  
Dense Core ◽  
Core Formation ◽  
Dense Core Vesicles ◽  
Atpase Subunit ◽  
Trans Golgi Network ◽  
Large Dense Core Vesicles ◽  
Golgi Network ◽  
Cargo Sorting

Large dense core vesicles (LDCVs) mediate the regulated release of neuropeptides and peptide hormones. They form at the trans-Golgi network (TGN), where their soluble content aggregates to form a dense core, but the mechanisms controlling biogenesis are still not completely understood. Recent studies have implicated the peripheral membrane protein HID-1 in neuropeptide sorting and insulin secretion. Using CRISPR/Cas9, we generated HID-1 KO rat neuroendocrine cells, and we show that the absence of HID-1 results in specific defects in peptide hormone and monoamine storage and regulated secretion. Loss of HID-1 causes a reduction in the number of LDCVs and affects their morphology and biochemical properties, due to impaired cargo sorting and dense core formation. HID-1 KO cells also exhibit defects in TGN acidification together with mislocalization of the Golgi-enriched vacuolar H+-ATPase subunit isoform a2. We propose that HID-1 influences early steps in LDCV formation by controlling dense core formation at the TGN.

Synaptotagmin-1: A Multi-Functional Protein that Mediates Vesicle Docking, Priming, and Fusion

2021 ◽  
Vol 22 ◽  
Author(s):  
Najeeb Ullah ◽  
Ezzouhra El Maaiden ◽  
Md. Sahab Uddin ◽  
Ghulam Md Ashraf
Keyword(s):  
Plasma Membrane ◽  
Secretory Granules ◽  
Secretory Vesicle ◽  
Neuroendocrine Cells ◽  
Snare Complex ◽  
Secretory Vesicles ◽  
Functional Protein ◽  
Vesicle Docking ◽  
Synaptotagmin 1

: The fusion of secretory vesicles with the plasma membrane depends on the assembly of v-SNAREs (VAMP2/synaptobrevin2) and t-SNAREs (SNAP25/syntaxin1) into the SNARE complex. Vesicles go through several upstream steps, referred to as docking and priming, to gain fusion competence. The vesicular protein synaptotagmin-1 (Syt-1) is the principal Ca2+ sensor for fusion in several central nervous system neurons and neuroendocrine cells and part of the docking complex for secretory granules. Syt-1 binds to the acceptor complex such as synaxin1, SNAP-25 on the plasma membrane to facilitate secretory vesicle docking, and upon Ca2+-influx promotes vesicle fusion. This review assesses the role of the Syt-1 protein involved in the secretory vesicle docking, priming, and fusion.

scholarly journals Trachynilysin mediates SNARE-dependent release of catecholamines from chromaffin cells via external and stored Ca2+

2000 ◽  
Vol 113 (7) ◽  
pp. 1119-1125 ◽  
Author(s):  
F.A. Meunier ◽  
C. Mattei ◽  
P. Chameau ◽  
G. Lawrence ◽  
C. Colasante ◽  
...  
Keyword(s):  
Chromaffin Cells ◽  
Motor Nerve ◽  
Neuroendocrine Cells ◽  
Dense Core ◽  
Frog Neuromuscular Junction ◽  
Dense Core Vesicles ◽  
Protein Receptor ◽  
Large Dense Core Vesicles ◽  
Quantal Transmitter Release ◽  
Bovine Chromaffin Cells

Trachynilysin, a 159 kDa dimeric protein purified from stonefish (Synanceia trachynis) venom, dramatically increases spontaneous quantal transmitter release at the frog neuromuscular junction, depleting small clear synaptic vesicles, whilst not affecting large dense core vesicles. The basis of this insensitivity of large dense core vesicles exocytosis was examined using a fluorimetric assay to determine whether the toxin could elicit catecholamine release from bovine chromaffin cells. Unlike the case of the motor nerve endings, nanomolar concentrations of trachynilysin evoked sustained Soluble N-ethylmaleimide-sensitive fusion protein Attachment Protein REceptor-dependent exocytosis of large dense core vesicles, but only in the presence of extracellular Ca2+. However, this response to trachynilysin does not rely on Ca2+ influx through voltage-activated Ca2+ channels because the secretion was only slightly affected by blockers of L, N and P/Q types. Instead, trachynilysin elicited a localized increase in intracellular fluorescence monitored with fluo-3/AM, that precisely co-localized with the increase of fluorescence resulting from caffeine-induced release of Ca2+ from intracellular stores. Moreover, depletion of the latter stores inhibited trachynilysin-induced exocytosis. Thus, the observed requirement of external Ca2+ for stimulation of large dense core vesicles exocytosis from chromaffin cells implicates plasma membrane channels that signal efflux of Ca2+ from intracellular stores. This study also suggests that the bases of exocytosis of large dense core vesicles from motor nerve terminals and neuroendocrine cells are distinct.

scholarly journals BAIAP3, a C2 domain–containing Munc13 protein, controls the fate of dense-core vesicles in neuroendocrine cells

2017 ◽  
Vol 216 (7) ◽  
pp. 2151-2166 ◽  
Author(s):  
Xingmin Zhang ◽  
Shan Jiang ◽  
Kelly A. Mitok ◽  
Lingjun Li ◽  
Alan D. Attie ◽  
...  
Keyword(s):  
Neuroendocrine Cells ◽  
Dense Core ◽  
Dense Core Vesicle ◽  
Protein Homeostasis ◽  
C2 Domain ◽  
Β Cells ◽  
Calcium Dependent ◽  
Trafficking Pathway ◽  
Protein Receptor ◽  
Golgi Network

Dense-core vesicle (DCV) exocytosis is a SNARE (soluble N-ethylmaleimide–sensitive fusion attachment protein receptor)-dependent anterograde trafficking pathway that requires multiple proteins for regulation. Several C2 domain–containing proteins are known to regulate Ca2+-dependent DCV exocytosis in neuroendocrine cells. In this study, we identified others by screening all (∼139) human C2 domain–containing proteins by RNA interference in neuroendocrine cells. 40 genes were identified, including several encoding proteins with known roles (CAPS [calcium-dependent activator protein for secretion 1], Munc13-2, RIM1, and SYT10) and many with unknown roles. One of the latter, BAIAP3, is a secretory cell–specific Munc13-4 paralog of unknown function. BAIAP3 knockdown caused accumulation of fusion-incompetent DCVs in BON neuroendocrine cells and lysosomal degradation (crinophagy) of insulin-containing DCVs in INS-1 β cells. BAIAP3 localized to endosomes was required for Golgi trans-Golgi network 46 (TGN46) recycling, exhibited Ca2+-stimulated interactions with TGN SNAREs, and underwent Ca2+-stimulated TGN recruitment. Thus, unlike other Munc13 proteins, BAIAP3 functions indirectly in DCV exocytosis by affecting DCV maturation through its role in DCV protein recycling. Ca2+ rises that stimulate DCV exocytosis may stimulate BAIAP3-dependent retrograde trafficking to maintain DCV protein homeostasis and DCV function.

Kiss and run exocytosis of dense core secretory vesicles

Neuroreport ◽  
2004 ◽  
Vol 15 (1) ◽  
pp. 79-81 ◽  
Author(s):  
Guy A. Rutter ◽  
Takashi Tsuboi
Keyword(s):  
Dense Core ◽  
Secretory Vesicles

scholarly journals Identification and characterization of a novel splicing variant of vesicular monoamine transporter 1

2005 ◽  
Vol 35 (3) ◽  
pp. 489-501 ◽  
Author(s):  
M Essand ◽  
S Vikman ◽  
J Grawé ◽  
L Gedda ◽  
C Hellberg ◽  
...  
Keyword(s):  
Neuroendocrine Cells ◽  
Vesicular Monoamine Transporter ◽  
Secretory Vesicles ◽  
Monoamine Transporter ◽  
Native Form ◽  
Biogenic Monoamines ◽  
Reading Frame ◽  
C Terminus ◽  
Large Dense Core Vesicles ◽  
Alternatively Spliced

Vesicular monoamine transporter 1 (VMAT1) is an integral protein in the membrane of secretory vesicles of neuroendocrine and endocrine cells that allows the transport of biogenic monoamines, such as serotonin, from the cytoplasm into the secretory vesicles. The full-length VMAT1 transcript is produced from 16 exons. We have identified and characterized an alternatively spliced form of VMAT1 that lacks exon 15, the next to last exon of VMAT1. The new form was therefore denoted VMAT1Δ15. Exon 15 does not contain an even multiple of three nucleotides. As a consequence, there is a shift of reading frame, and exon 16 is translated in an alternative reading frame, yielding a novel protein with a shorter and unrelated C-terminus compared with the native VMAT1 protein. VMAT1 and VMAT1Δ15 mRNAs are simultaneously expressed in normal and neoplastic neuroendocrine cells of the GI tract. However, VMAT1 expression is always higher than VMAT1Δ15 expression. We prove that VMAT1Δ15 is not localized in large, dense core vesicles as the native form but in the endoplasmic reticulum. Furthermore, while VMAT1 can take up serotonin, VMAT1Δ15 cannot, indicating different functions for the two forms of VMAT1.

Sign in / Sign up

Export Citation Format

Share Document