Secretory Granule Exocytosis

2003 ◽  
Vol 83 (2) ◽  
pp. 581-632 ◽  
Author(s):  
Robert D. Burgoyne ◽  
Alan Morgan
Keyword(s):  
Secretory Granule ◽  
Secretory Granules ◽  
Physiological Role ◽  
Cell Types ◽  
Control Mechanisms ◽  
Granule Exocytosis ◽  
Synaptic Vesicle Exocytosis ◽  
Wide Range ◽  
Vesicle Exocytosis ◽  
Protein Components

Regulated exocytosis of secretory granules or dense-core granules has been examined in many well-characterized cell types including neurons, neuroendocrine, endocrine, exocrine, and hemopoietic cells and also in other less well-studied cell types. Secretory granule exocytosis occurs through mechanisms with many aspects in common with synaptic vesicle exocytosis and most likely uses the same basic protein components. Despite the widespread expression and conservation of a core exocytotic machinery, many variations occur in the control of secretory granule exocytosis that are related to the specialized physiological role of particular cell types. In this review we describe the wide range of cell types in which regulated secretory granule exocytosis occurs and assess the evidence for the expression of the conserved fusion machinery in these cells. The signals that trigger and regulate exocytosis are reviewed. Aspects of the control of exocytosis that are specific for secretory granules compared with synaptic vesicles or for particular cell types are described and compared to define the range of accessory control mechanisms that exert their effects on the core exocytotic machinery.

scholarly journals Melanophilin accelerates insulin granule fusion without predocking to the plasma membrane

2020 ◽  
Author(s):  
Ada Admin ◽  
Hao Wang ◽  
Kouichi Mizuno ◽  
Noriko Takahashi ◽  
Eri Kobayashi ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Secretory Granule ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Granule Exocytosis ◽  
Synaptic Vesicle Exocytosis ◽  
Granule Membrane ◽  
Myosin Va ◽  
Vesicle Exocytosis ◽  
Glucose Stimulated Insulin Secretion

Direct observation of fluorescence-labeled secretory granule exocytosis in living pancreatic β cells has revealed heterogeneous prefusion behaviors: some granules dwell beneath the plasma membrane before fusion, while others fuse immediately once they are recruited to the plasma membrane. Although the former mode seems to follow sequential docking-priming-fusion steps as found in synaptic vesicle exocytosis, the latter mode, which is unique to secretory granule exocytosis, has not been explored well. Here, we show that melanophilin, one of the effectors of the monomeric GTPase Rab27 on the granule membrane, is involved in such an accelerated mode of exocytosis. Both melanophilin-mutated <i>leaden</i> mouse and melanophilin-downregulated human pancreatic β cells exhibit impaired glucose-stimulated insulin secretion, with a specific reduction in fusion events that bypass stable docking to the plasma membrane. Upon stimulus-induced [Ca<sup>2+</sup>]<sub>i</sub> rise, melanophilin mediates this type of fusion by dissociating granules from myosin-Va and actin in the actin cortex and by associating them with a fusion-competent, open form of syntaxin-4 on the plasma membrane. These findings provide the hitherto unknown mechanism to support sustainable exocytosis by which granules are recruited from the cell interior and fuse promptly without stable predocking to the plasma membrane.

scholarly journals Melanophilin accelerates insulin granule fusion without predocking to the plasma membrane

2020 ◽  
Author(s):  
Ada Admin ◽  
Hao Wang ◽  
Kouichi Mizuno ◽  
Noriko Takahashi ◽  
Eri Kobayashi ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Secretory Granule ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Granule Exocytosis ◽  
Synaptic Vesicle Exocytosis ◽  
Granule Membrane ◽  
Myosin Va ◽  
Vesicle Exocytosis ◽  
Glucose Stimulated Insulin Secretion

Direct observation of fluorescence-labeled secretory granule exocytosis in living pancreatic β cells has revealed heterogeneous prefusion behaviors: some granules dwell beneath the plasma membrane before fusion, while others fuse immediately once they are recruited to the plasma membrane. Although the former mode seems to follow sequential docking-priming-fusion steps as found in synaptic vesicle exocytosis, the latter mode, which is unique to secretory granule exocytosis, has not been explored well. Here, we show that melanophilin, one of the effectors of the monomeric GTPase Rab27 on the granule membrane, is involved in such an accelerated mode of exocytosis. Both melanophilin-mutated <i>leaden</i> mouse and melanophilin-downregulated human pancreatic β cells exhibit impaired glucose-stimulated insulin secretion, with a specific reduction in fusion events that bypass stable docking to the plasma membrane. Upon stimulus-induced [Ca<sup>2+</sup>]<sub>i</sub> rise, melanophilin mediates this type of fusion by dissociating granules from myosin-Va and actin in the actin cortex and by associating them with a fusion-competent, open form of syntaxin-4 on the plasma membrane. These findings provide the hitherto unknown mechanism to support sustainable exocytosis by which granules are recruited from the cell interior and fuse promptly without stable predocking to the plasma membrane.

scholarly journals Melanophilin accelerates insulin granule fusion without predocking to the plasma membrane

2020 ◽  
Author(s):  
Ada Admin ◽  
Hao Wang ◽  
Kouichi Mizuno ◽  
Noriko Takahashi ◽  
Eri Kobayashi ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Secretory Granule ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Granule Exocytosis ◽  
Synaptic Vesicle Exocytosis ◽  
Granule Membrane ◽  
Myosin Va ◽  
Vesicle Exocytosis ◽  
Glucose Stimulated Insulin Secretion

Direct observation of fluorescence-labeled secretory granule exocytosis in living pancreatic β cells has revealed heterogeneous prefusion behaviors: some granules dwell beneath the plasma membrane before fusion, while others fuse immediately once they are recruited to the plasma membrane. Although the former mode seems to follow sequential docking-priming-fusion steps as found in synaptic vesicle exocytosis, the latter mode, which is unique to secretory granule exocytosis, has not been explored well. Here, we show that melanophilin, one of the effectors of the monomeric GTPase Rab27 on the granule membrane, is involved in such an accelerated mode of exocytosis. Both melanophilin-mutated <i>leaden</i> mouse and melanophilin-downregulated human pancreatic β cells exhibit impaired glucose-stimulated insulin secretion, with a specific reduction in fusion events that bypass stable docking to the plasma membrane. Upon stimulus-induced [Ca<sup>2+</sup>]<sub>i</sub> rise, melanophilin mediates this type of fusion by dissociating granules from myosin-Va and actin in the actin cortex and by associating them with a fusion-competent, open form of syntaxin-4 on the plasma membrane. These findings provide the hitherto unknown mechanism to support sustainable exocytosis by which granules are recruited from the cell interior and fuse promptly without stable predocking to the plasma membrane.

scholarly journals Lectinocytochemical specificity in human eosinophils and neutrophils: a reexamination.

1991 ◽  
Vol 39 (9) ◽  
pp. 1157-1166 ◽  
Author(s):  
W B VanWinkle
Keyword(s):  
Thin Section ◽  
Specific Binding ◽  
Secretory Granules ◽  
Cell Types ◽  
Specimen Preparation ◽  
Electron Microscopic ◽  
Wet Chemical ◽  
Eosinophil Granule ◽  
Protein Components ◽  
Labeling Pattern

As with secretory granules in other cell types, many of the protein components that make up the cytoplasmic granules of human leukocytes are glycoproteins. It is not unexpected, therefore, that lectins specific for various carbohydrate moieties can be localized in these granules following appropriate protocols for specimen preparation and thin-section labeling. In this study, isolated human eosinophils and neutrophils were prepared for lectin-gold electron microscopic localization by procedures that involve no exposure to aqueous fixatives, buffers, or solvents (rapid cryofixation and molecular distillation drying), thus removing the potential problem of constituent extraction or translocation during so-called "wet chemical" processing. In contrast to other reports, data presented illustrate the specific binding of soybean agglutinin (SBA) to eosinophil granule matrices (not the crystalline cores), as well as to a population of granules in neutrophils. A similar labeling pattern for wheat germ agglutinin (WGA) was also seen, confirming the presence of N-acetyl-D-galactosamine and N-acetyl-D-glucosamine residues in eosinophil and neutrophil granule matrices. These studies emphasize the need for carefully designed specimen preparation as well as subsequent thin-section labeling procedures in lectinocytochemical studies.

scholarly journals Diverse modes of synaptic signaling, regulation, and plasticity distinguish two classes of C. elegans glutamatergic neurons

2017 ◽  
Author(s):  
Donovan Ventimiglia ◽  
Cornelia I. Bargmann
Keyword(s):  
Synaptic Vesicle ◽  
Neuronal Cell ◽  
Cell Types ◽  
Snare Complex ◽  
C Elegans ◽  
Synaptic Vesicle Exocytosis ◽  
High Calcium ◽  
Vesicle Exocytosis ◽  
Synaptic Dynamics

AbstractSynaptic vesicle release properties vary between neuronal cell types, but in most cases the molecular basis of this heterogeneity is unknown. Here, we compare in vivo synaptic properties of two neuronal classes in the C. elegans central nervous system, using VGLUT-pHluorin to monitor synaptic vesicle exocytosis and retrieval in intact animals. We show that the glutamatergic sensory neurons AWCON and ASH have distinct synaptic dynamics associated with tonic and phasic synaptic properties, respectively. Exocytosis in ASH and AWCON is differentially affected by SNARE-complex regulators that are present in both neurons: phasic ASH release is strongly dependent on UNC-13, whereas tonic AWCON release relies upon UNC-18 and on the protein kinase C homolog PKC-1. Exocytosis and retrieval each have two timescales in AWCON but one major timescale in ASH. Strong stimuli that elicit high calcium levels also increase exocytosis and retrieval rates in AWCON, generating distinct tonic and evoked synaptic modes. These results highlight the differential deployment of shared presynaptic proteins in neuronal cell type-specific functions.

Two proteins associated with secretory granule membranes identified in chicken regulated secretory cells

1994 ◽  
Vol 107 (5) ◽  
pp. 1297-1308
Author(s):  
J.L. Thomas ◽  
A. Stieber ◽  
N. Gonatas
Keyword(s):  
Secretory Granule ◽  
Secretory Pathway ◽  
Secretory Granules ◽  
Cell Types ◽  
Pancreatic Acinar Cells ◽  
Secretory Cells ◽  
Electrophoretic Patterns ◽  
Granule Membrane ◽  
The Central Nervous System ◽  
Ultrathin Frozen Sections

Lately, we have identified two polypeptides of 92–94 kDa (GRL1) and 45–60 kDa (GRL2), expressed in cytoplasmic granules of chicken granulocytes and thrombocytes. Here, we report that GRL1 and GRL2 are widely distributed in all exocrine and several endocrine cell types, but not in neurons of the central nervous system, during late stages of embryonic development, as well as in newly hatched and two-month-old chickens. Immunogold studies in ultrathin frozen sections of pancreatic acinar cells show that GRL1 and GRL2 are co-localized at the periphery of zymogen granules, in granules fused with apical acinar membranes and on apical membranes of acini, while the pregranular compartments of the secretory pathway are weakly or not labeled. Semiquantitative morphometric studies indicate that GRL1 and GRL2 are equally distributed in secretory granules. A variety of physical and metabolic studies reveal that GRL2, a highly N-glycosylated polypeptide, is an intrinsic membrane protein, while GRL1 is a peripheral membrane polypeptide released by Na2CO3 treatment of granulocyte membranes. In all hematopoietic, exocrine or endocrine cells examinated, GRL1 shows identical electrophoretic patterns, while GRL2 is identified as a diffuse band, at 40–65 kDa, in hematopoietic and pancreatic cells. Taken together, the morphological and biochemical studies indicate that GRL1 and GRL2 are components of the secretory granule membrane in chicken exocrine, endocrine and hemopoietic cell types.

scholarly journals Stable and Flexible Synaptic Transmission Controlled by the Active Zone Protein Interactions

2021 ◽  
Vol 22 (21) ◽  
pp. 11775
Author(s):  
Sumiko Mochida
Keyword(s):  
Synaptic Transmission ◽  
Protein Interactions ◽  
Active Zone ◽  
Synaptic Vesicles ◽  
Physiological Role ◽  
Release Site ◽  
Synaptic Vesicle Exocytosis ◽  
Vesicle Exocytosis ◽  
Presynaptic Plasma Membrane ◽  
Sensor Proteins

An action potential triggers neurotransmitter release from synaptic vesicles docking to a specialized release site of the presynaptic plasma membrane, the active zone. The active zone is a highly organized structure with proteins that serves as a platform for synaptic vesicle exocytosis, mediated by SNAREs complex and Ca2+ sensor proteins, within a sub-millisecond opening of nearby Ca2+ channels with the membrane depolarization. In response to incoming neuronal signals, each active zone protein plays a role in the release-ready site replenishment with synaptic vesicles for sustainable synaptic transmission. The active zone release apparatus provides a possible link between neuronal activity and plasticity. This review summarizes the mostly physiological role of active zone protein interactions that control synaptic strength, presynaptic short-term plasticity, and homeostatic synaptic plasticity.

scholarly journals Diverse modes of synaptic signaling, regulation, and plasticity distinguish two classes of C. elegans glutamatergic neurons

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Donovan Ventimiglia ◽  
Cornelia I Bargmann
Keyword(s):  
Synaptic Vesicle ◽  
Neuronal Cell ◽  
Cell Types ◽  
Snare Complex ◽  
C Elegans ◽  
Synaptic Vesicle Exocytosis ◽  
High Calcium ◽  
Vesicle Exocytosis ◽  
Synaptic Dynamics

Synaptic vesicle release properties vary between neuronal cell types, but in most cases the molecular basis of this heterogeneity is unknown. Here, we compare in vivo synaptic properties of two neuronal classes in the C. elegans central nervous system, using VGLUT-pHluorin to monitor synaptic vesicle exocytosis and retrieval in intact animals. We show that the glutamatergic sensory neurons AWCON and ASH have distinct synaptic dynamics associated with tonic and phasic synaptic properties, respectively. Exocytosis in ASH and AWCON is differentially affected by SNARE-complex regulators that are present in both neurons: phasic ASH release is strongly dependent on UNC-13, whereas tonic AWCON release relies upon UNC-18 and on the protein kinase C homolog PKC-1. Strong stimuli that elicit high calcium levels increase exocytosis and retrieval rates in AWCON, generating distinct tonic and evoked synaptic modes. These results highlight the differential deployment of shared presynaptic proteins in neuronal cell type-specific functions.

Definition of Munc13-homology-domains and characterization of a novel ubiquitously expressed Munc13 isoform

2000 ◽  
Vol 349 (1) ◽  
pp. 247-253 ◽  
Author(s):  
Henriette KOCH ◽  
Kay HOFMANN ◽  
Nils BROSE
Keyword(s):  
Membrane Trafficking ◽  
Expressed Sequence Tag ◽  
Bronchial Epithelium ◽  
Cell Types ◽  
Alveolar Type ◽  
Novel Proteins ◽  
Synaptic Vesicle Exocytosis ◽  
Vesicle Exocytosis ◽  
Definition Of ◽  
Homology Domains

Munc13 proteins constitute a family of three highly homologous molecules (Munc13-1, Munc13-2 and Munc13-3). With the exception of a ubiquitously expressed Munc13-2 splice variant, Munc13 proteins are brain-specific. Munc13-1 has a central priming function in synaptic vesicle exocytosis from glutamatergic synapses. In order to identify Munc13-like proteins that may regulate secretory processes in non-glutamatergic neurons or non-neuronal cells, we developed protein profiles for two Munc13-homology-domains (MHDs). MHDs are present in a wide variety of proteins, some of which have previously been implicated in membrane trafficking reactions. Taking advantage of partial sequences in the human expressed sequence tag (EST) database, we characterized a novel, ubiquitously expressed, rat protein (Munc13-4) that belongs to a subfamily of Munc13-like molecules, in which the typical Munc13-like domain structure is conserved. Munc13-4 is predominantly expressed in lung where it is localized to goblet cells of the bronchial epithelium and to alveolar type II cells, both of which are cell types with secretory function. In the present study we identify a group of novel proteins, some of which may function in a Munc13-like manner to regulate membrane trafficking. The MHD profiles described in the present study are useful tools for the identification of Munc13-like proteins, that would otherwise have remained undetected.

scholarly journals Synaptotagmin VII Regulates Ca2+-Dependent Exocytosis of Lysosomes in Fibroblasts

2000 ◽  
Vol 148 (6) ◽  
pp. 1141-1150 ◽  
Author(s):  
Iñigo Martinez ◽  
Sabyasachi Chakrabarti ◽  
Turid Hellevik ◽  
Jennifer Morehead ◽  
Kimberly Fowler ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Rat Kidney ◽  
Transmembrane Proteins ◽  
Cell Types ◽  
C2 Domains ◽  
Synaptic Vesicle Exocytosis ◽  
Vesicle Exocytosis ◽  
Normal Rat ◽  
Recombinant Fragments ◽  
C2a Domain

Synaptotagmins (Syts) are transmembrane proteins with two Ca2+-binding C2 domains in their cytosolic region. Syt I, the most widely studied isoform, has been proposed to function as a Ca2+ sensor in synaptic vesicle exocytosis. Several of the twelve known Syts are expressed primarily in brain, while a few are ubiquitous (Sudhof, T.C., and J. Rizo. 1996. Neuron. 17: 379–388; Butz, S., R. Fernandez-Chacon, F. Schmitz, R. Jahn, and T.C. Sudhof. 1999. J. Biol. Chem. 274:18290–18296). The ubiquitously expressed Syt VII binds syntaxin at free Ca2+ concentrations ([Ca2+]) below 10 μM, whereas other isoforms require 200–500 μM [Ca2+] or show no Ca2+-dependent syntaxin binding (Li, C., B. Ullrich, Z. Zhang, R.G.W. Anderson, N. Brose, and T.C. Sudhof. 1995. Nature. 375:594–599). We investigated the involvement of Syt VII in the exocytosis of lysosomes, which is triggered in several cell types at 1–5 μM [Ca2+] (Rodríguez, A., P. Webster, J. Ortego, and N.W. Andrews. 1997. J. Cell Biol. 137:93–104). Here, we show that Syt VII is localized on dense lysosomes in normal rat kidney (NRK) fibroblasts, and that GFP-tagged Syt VII is targeted to lysosomes after transfection. Recombinant fragments containing the C2A domain of Syt VII inhibit Ca2+-triggered secretion of β-hexosaminidase and surface translocation of Lgp120, whereas the C2A domain of the neuronal- specific isoform, Syt I, has no effect. Antibodies against the Syt VII C2A domain are also inhibitory in both assays, indicating that Syt VII plays a key role in the regulation of Ca2+-dependent lysosome exocytosis.

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