scholarly journals What the granins tell us about the formation of secretory granules in neuroendocrine cells

1991 ◽  
Vol 19 (1) ◽  
Author(s):  
Eric Chanat ◽  
Sanjay W. Pimplikar ◽  
Jane C. Stinchcombe ◽  
Wieland B. Huttner
Keyword(s):  
Secretory Granules ◽  
Neuroendocrine Cells

Synaptic Transmission in the Immune System

e-Neuroforum ◽  
2017 ◽  
Vol 23 (4) ◽  
Author(s):  
Jens Rettig ◽  
David R. Stevens
Keyword(s):  
Nervous System ◽  
Immune System ◽  
Synaptic Transmission ◽  
Molecular Mechanisms ◽  
Secretory Granules ◽  
Neuroendocrine Cells ◽  
Regulated Exocytosis ◽  
Protein Receptor ◽  
Immunological Synapses ◽  
Immunological Diseases

AbstractThe release of neurotransmitters at synapses belongs to the most important processes in the central nervous system. In the last decades much has been learned about the molecular mechanisms which form the basis for this fundamental process. Highly regulated exocytosis, based on the SNARE (soluble N-ethylmaleimide-sensitive attachment protein receptor) complex and its regulatory molecules is the signature specialization of the nervous system and is shared by neurons and neuroendocrine cells. Cells of the immune system use a similar mechanism to release cytotoxic materials from secretory granules at contacts with virally or bacterially infected cells or cancer cells, in order to remove these threats. These contact zones have been termed immunological synapses in reference to the highly specific targeted exocytosis of effector molecules. Recent findings indicate that mutations in SNARE or SNARE-interacting proteins are the basis of a number of devastating immunological diseases. While SNARE complexes are ubiquitous and mediate a wide variety of membrane fusion events it is surprising that in many cases the SNARE proteins involved in immunological synapses are the same molecules which mediate regulated exocytosis of transmitters and hormones in neurons and neuroendocrine cells. These similarities raise the possibility that results obtained at immunological synapses may be applicable, in particular in the area of presynaptic function, to neuronal synapses. Since immunological synapses (IS) are assembled and disassembled in about a half an hour, the use of immune cells isolated from human blood allows not only the study of the molecular mechanisms of synaptic transmission in human cells, but is particularly suited to the examination of the assembly and disassembly of these “synapses” via live imaging. In this overview we discuss areas of similarity between synapses of the nervous and immune systems and in the process will refer to results of our experiments of the last few years.

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.

Biogenesis and Transport of Secretory Granules to Release Site in Neuroendocrine Cells

2008 ◽  
Vol 37 (2) ◽  
pp. 151-159 ◽  
Author(s):  
Joshua J. Park ◽  
Hisatsugu Koshimizu ◽  
Y. Peng Loh
Keyword(s):  
Secretory Granules ◽  
Release Site ◽  
Neuroendocrine Cells

scholarly journals Chromogranin A Induces the Biogenesis of Granules with Calcium- and Actin-Dependent Dynamics and Exocytosis in Constitutively Secreting Cells

Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4444-4456 ◽  
Author(s):  
Salah Elias ◽  
Charlène Delestre ◽  
Stéphane Ory ◽  
Sébastien Marais ◽  
Maïté Courel ◽  
...  
Keyword(s):  
Molecular Motors ◽  
Chromogranin A ◽  
Molecular Mechanisms ◽  
Secretory Granules ◽  
Active Role ◽  
Subcellular Fractionation ◽  
Neuroendocrine Cells ◽  
Cortical Actin ◽  
Neuropeptide Secretion ◽  
Granule Membrane

Chromogranins are a family of acidic glycoproteins that play an active role in hormone and neuropeptide secretion through their crucial role in secretory granule biogenesis in neuroendocrine cells. However, the molecular mechanisms underlying their granulogenic activity are still not fully understood. Because we previously demonstrated that the expression of the major component of secretory granules, chromogranin A (CgA), is able to induce the formation of secretory granules in nonendocrine COS-7 cells, we decided to use this model to dissect the mechanisms triggered by CgA leading to the biogenesis and trafficking of such granules. Using quantitative live cell imaging, we first show that CgA-induced organelles exhibit a Ca2+-dependent trafficking, in contrast to native vesicle stomatitis virus G protein-containing constitutive vesicles. To identify the proteins that confer such properties to the newly formed granules, we developed CgA-stably-expressing COS-7 cells, purified their CgA-containing granules by subcellular fractionation, and analyzed the granule proteome by liquid chromatography-tandem mass spectrometry. This analysis revealed the association of several cytosolic proteins to the granule membrane, including GTPases, cytoskeleton-based molecular motors, and other proteins with actin- and/or Ca2+-binding properties. Furthermore, disruption of cytoskeleton affects not only the distribution and the transport but also the Ca2+-evoked exocytosis of the CgA-containing granules, indicating that these granules interact with microtubules and cortical actin for the regulated release of their content. These data demonstrate for the first time that the neuroendocrine factor CgA induces the recruitment of cytoskeleton-, GTP-, and Ca2+-binding proteins in constitutively secreting COS-7 cells to generate vesicles endowed with typical dynamics and exocytotic properties of neuroendocrine secretory granules.

scholarly journals Physiological manipulation of cellular activity tunes protein and ultrastructural profiles in a neuroendocrine cell

2008 ◽  
Vol 198 (3) ◽  
pp. 607-616 ◽  
Author(s):  
François van Herp ◽  
Nick H M van Bakel ◽  
Anton J M Coenen ◽  
Kjell Sergeant ◽  
Bart Devreese ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Secretory Granules ◽  
Neuroendocrine Cells ◽  
Neuroendocrine Cell ◽  
Gradual Transition ◽  
Secretory Proteins ◽  
Cellular Activity ◽  
Scanning Electron

To study in vivo the dynamics of the biosynthetic and secretory processes in a neuroendocrine cell, we use the proopiomelanocortin-producing intermediate pituitary melanotrope cells of Xenopus laevis. The activity of these cells can be simply manipulated by adapting the animal to a white or a black background, resulting in inactive and hyperactive cells respectively. Here, we applied differential display proteomics and field emission scanning electron microscopy (FESEM) to examine the changes in architecture accompanying the gradual transition of the inactive to the hyperactive melanotrope cells. The proteomic analysis showed differential expression of neuroendocrine secretory proteins, endoplasmic reticulum (ER)-resident chaperones, and housekeeping and metabolic proteins. The FESEM study revealed changes in the ultrastructure of the ER and Golgi and the number of secretory granules. We conclude that activation of neuroendocrine cells tunes their molecular machineries and organelles to become professional secretors.

scholarly journals Novel organelle anion channels formed by chromogranin B drive normal granule maturation in endocrine cells

2018 ◽  
Author(s):  
Gaya Yadav ◽  
Hui Zheng ◽  
Qing Yang ◽  
Lauren Douma ◽  
Mani Annamalai ◽  
...  
Keyword(s):  
Pancreatic Beta Cells ◽  
Chloride Channels ◽  
Endocrine Cells ◽  
Secretory Granules ◽  
Neuroendocrine Cells ◽  
Anion Channels ◽  
Chromogranin B ◽  
Fast Kinetics ◽  
Anion Conductance ◽  
Granule Maturation

All endocrine cells need an anion conductance for maturation of secretory granules. Identity of this family of anion channels has been elusive for forty years. We now show that a family of granule proteins, CHGB, serves the long-sought conductance. CHGB interacts with membranes through two amphipathic helices, and forms a chloride channel with a large conductance and high anion selectivity. Fast kinetics and high cooperativity suggest that CHGB tetramerizes to form a functional channel. Nonconducting mutants separate CHGB channel function in granule maturation from its role in granule biogenesis. In neuroendocrine cells, CHGB channel and a H+-ATPase drive normal insulin maturation inside or catecholamine loading into secretory granules. Tight membrane-association of CHGB after exocytotic release of secretory granules separates its intracellular functions from the extracellular functions accomplished by its proteolytic peptides. CHGB-null mice show impairment of granule acidification in pancreatic beta-cells due to lack of anion conductance. These findings together support that the phylogenetically conserved CHGB proteins constitute a fifth family of chloride channels that function in various endocrine cells.

scholarly journals Localization of integral membrane peptidylglycine alpha-amidating monooxygenase in neuroendocrine cells

1997 ◽  
Vol 110 (6) ◽  
pp. 695-706 ◽  
Author(s):  
S.L. Milgram ◽  
S.T. Kho ◽  
G.V. Martin ◽  
R.E. Mains ◽  
B.A. Eipper
Keyword(s):  
Steady State ◽  
Secretory Granules ◽  
Microscopic Level ◽  
Neuroendocrine Cells ◽  
Light Microscopic Level ◽  
Steady State Distribution ◽  
State Distribution ◽  
Golgi Membranes ◽  
Early Endosomes ◽  
Golgi Network

Peptidylglycine alpha-amidating monooxygenase (PAM) catalyzes the amidation of glycine-extended peptides in neuroendocrine cells. At steady state, membrane PAM is accumulated in a perinuclear compartment. We examined the distribution of membrane PAM in stably transfected AtT-20 cells and compared its localization to markers for the trans-Golgi network (TGN), endosomes, and lysosomes. At the light microscopic level, the distribution of membrane PAM does not overlap extensively with lysosomal markers but does overlap with TGN38 and with SCAMP, a component of post-Golgi membranes involved in recycling pathways. By immunoelectron microscopy, membrane PAM is present in tubulovesicular structures which constitute the TGN; some of these PAM-containing tubulovesicular structures are more distal to the Golgi stacks and do not contain TGN38. While some POMC-derived peptides are present in tubulovesicular structures like those that contain membrane PAM, the majority of the POMC-derived peptides are present in secretory granules. There is little overlap between the steady state distribution of membrane PAM and internalized FITC-transferrin in the early endosomes. Few of the perinuclear PAM-containing structures are labeled with HRP or WGA-HRP even following long incubations. Therefore, membrane PAM is localized to perinuclear tubulovesicular structures which are partially devoid of TGN38 and are not all endosomal in origin.

scholarly journals Electron microscopic localization of chromogranin A in osmium-fixed neuroendocrine cells with a protein A-gold technique.

1987 ◽  
Vol 35 (7) ◽  
pp. 795-801 ◽  
Author(s):  
S A Hearn
Keyword(s):  
Neuroendocrine Tumors ◽  
Chromogranin A ◽  
Osmium Tetroxide ◽  
Secretory Granules ◽  
Protein A ◽  
Neuroendocrine Cells ◽  
Neurosecretory Granules ◽  
Electron Microscopic ◽  
Thin Sections ◽  
Carotid Body Tumors

An antibody (LK2H10) to chromogranin A has been recommended for use in ultrastructural identification of neuroendocrine secretory granules. Previous studies have demonstrated immunoreactive chromogranin A in specimens prepared for electron microscopy by glutaraldehyde fixation only. In this study, the effect of specimen post-fixation by osmium tetroxide on post-embedding localization of chromogranin A was evaluated. Human tissues from benign endocrine glands, neuroendocrine tumors, and non-neuroendocrine tumors were post-fixed in osmium, embedded in epoxy resin, and the sample thin sections immunolabeled using a protein A-gold technique. Chromogranin A-positive neurosecretory granules were detected in pancreatic islets, adrenal medulla, stomach, ileum, anterior pituitary, and parathyroid. Mid-gut carcinoids, bronchial carcinoids, pheochromocytomas, paragangliomas, carotid body tumors, and thyroid medullary carcinomas contained immunoreactive granules. Cytoplasmic granules in non-neuroendocrine tumors did not react for chromogranin A. Tissues post-fixed in osmium tetroxide had optimally preserved ultrastructural features, and use of this fixative is compatible with postembedding localization of chromogranin A in neurosecretory granules.

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