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Theranostics 2021As extracellular vesicles secreted by cells, exosomes are intercellular signalosomes for cell communication and pharmacological effectors. Because of their special... (Review)
Review
As extracellular vesicles secreted by cells, exosomes are intercellular signalosomes for cell communication and pharmacological effectors. Because of their special properties, including low toxicity and immunogenicity, biodegradability, ability to encapsulate endogenous biologically active molecules and cross the blood-brain barrier (BBB), exosomes have great therapeutic potential in cerebrovascular and neurodegenerative diseases. However, the poor targeting ability of natural exosomes greatly reduces the therapeutic effect. Using engineering technology, exosomes can obtain active targeting ability to accumulate in specific cell types and tissues by attaching targeting units to the membrane surface or loading them into cavities. In this review, we outline the improved targeting functions of bioengineered exosomes, tracing and imaging techniques, administration methods, internalization in the BBB, and therapeutic effects of exosomes in cerebrovascular and neurodegenerative diseases and further evaluate the clinical opportunities and challenges in this research field.
Topics: Animals; Bioengineering; Biological Transport; Blood-Brain Barrier; Cell Communication; Cerebrovascular Disorders; Drug Delivery Systems; Exosomes; Extracellular Vesicles; Humans; Neurodegenerative Diseases; Protein Engineering; Secretory Vesicles
PubMed: 34522219
DOI: 10.7150/thno.62330 -
Annual Review of Microbiology 2010Gram-negative bacteria produce outer membrane vesicles (OMVs) that contain biologically active proteins and perform diverse biological processes. Unlike other secretion... (Review)
Review
Gram-negative bacteria produce outer membrane vesicles (OMVs) that contain biologically active proteins and perform diverse biological processes. Unlike other secretion mechanisms, OMVs enable bacteria to secrete insoluble molecules in addition to and in complex with soluble material. OMVs allow enzymes to reach distant targets in a concentrated, protected, and targeted form. OMVs also play roles in bacterial survival: Their production is a bacterial stress response and important for nutrient acquisition, biofilm development, and pathogenesis. Key characteristics of OMV biogenesis include outward bulging of areas lacking membrane-peptidoglycan bonds, the capacity to upregulate vesicle production without also losing outer membrane integrity, enrichment or exclusion of certain proteins and lipids, and membrane fission without direct energy from ATP/GTP hydrolysis. Comparisons of similar budding mechanisms from diverse biological domains have provided new insight into evaluating mechanisms for outer membrane vesiculation.
Topics: Bacterial Proteins; Cell Membrane; Gram-Negative Bacteria; Secretory Vesicles
PubMed: 20825345
DOI: 10.1146/annurev.micro.091208.073413 -
Cellular and Molecular Life Sciences :... Mar 2021Insulin is produced by pancreatic β-cells, and once released to the blood, the hormone stimulates glucose uptake and suppresses glucose production. Defects in both the... (Review)
Review
Insulin is produced by pancreatic β-cells, and once released to the blood, the hormone stimulates glucose uptake and suppresses glucose production. Defects in both the availability and action of insulin lead to elevated plasma glucose levels and are major hallmarks of type-2 diabetes. Insulin is stored in secretory granules that form at the trans-Golgi network. The granules undergo extensive modifications en route to their release sites at the plasma membrane, including changes in both protein and lipid composition of the granule membrane and lumen. In parallel, the insulin molecules also undergo extensive modifications that render the hormone biologically active. In this review, we summarize current understanding of insulin secretory granule biogenesis, maturation, transport, docking, priming and eventual fusion with the plasma membrane. We discuss how different pools of granules form and how these pools contribute to insulin secretion under different conditions. We also highlight the role of the β-cell in the development of type-2 diabetes and discuss how dysregulation of one or several steps in the insulin granule life cycle may contribute to disease development or progression.
Topics: Animals; Biological Transport; Blood Glucose; Cell Membrane; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Secretion; Insulin-Secreting Cells; Secretory Vesicles
PubMed: 33146746
DOI: 10.1007/s00018-020-03688-4 -
Biochimica Et Biophysica Acta.... Dec 2020
Topics: Amino Acid Transport Systems; Animals; Humans; Lysosomes; Membrane Transport Proteins; Organelles; Secretory Vesicles
PubMed: 32861642
DOI: 10.1016/j.bbamem.2020.183458 -
Cellular and Molecular Life Sciences :... Jan 2023At the onset of Drosophila metamorphosis, plenty of secretory glue granules are released from salivary gland cells and the glue is deposited on the ventral side of the...
At the onset of Drosophila metamorphosis, plenty of secretory glue granules are released from salivary gland cells and the glue is deposited on the ventral side of the forming (pre)pupa to attach it to a dry surface. Prior to this, a poorly understood maturation process takes place during which secretory granules gradually grow via homotypic fusions, and their contents are reorganized. Here we show that the small GTPase Rab26 localizes to immature (smaller, non-acidic) glue granules and its presence prevents vesicle acidification. Rab26 mutation accelerates the maturation, acidification and release of these secretory vesicles as well as the lysosomal breakdown (crinophagy) of residual, non-released glue granules. Strikingly, loss of Mon1, an activator of the late endosomal and lysosomal fusion factor Rab7, results in Rab26 remaining associated even with the large glue granules and a concomitant defect in glue release, similar to the effects of Rab26 overexpression. Our data thus identify Rab26 as a key regulator of secretory vesicle maturation that promotes early steps (vesicle growth) and inhibits later steps (lysosomal transport, acidification, content reorganization, release, and breakdown), which is counteracted by Mon1.
Topics: Animals; Drosophila; Drosophila Proteins; Lysosomes; rab GTP-Binding Proteins; Salivary Glands; Secretory Vesicles
PubMed: 36600084
DOI: 10.1007/s00018-022-04674-8 -
Physiological Reviews Apr 2003Regulated exocytosis of secretory granules or dense-core granules has been examined in many well-characterized cell types including neurons, neuroendocrine, endocrine,... (Review)
Review
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.
Topics: Animals; Exocytosis; Humans; Secretory Vesicles; Signal Transduction
PubMed: 12663867
DOI: 10.1152/physrev.00031.2002 -
Platelets Mar 2017
Topics: Blood Platelets; Hematology; History, 20th Century; History, 21st Century; Humans; Secretory Vesicles; Workforce
PubMed: 28281920
DOI: 10.1080/09537104.2016.1277676 -
Blood Feb 2022
Topics: Megakaryocytes; Secretory Vesicles
PubMed: 35142851
DOI: 10.1182/blood.2021015053 -
Biomolecules Sep 2021Until recently, astrocytes were thought to be a part of a simple "brain glue" providing only a supporting role for neurons. However, the discoveries of the last two... (Review)
Review
Until recently, astrocytes were thought to be a part of a simple "brain glue" providing only a supporting role for neurons. However, the discoveries of the last two decades have proven astrocytes to be dynamic partners participating in brain metabolism and actively influencing communication between neurons. The means of astrocyte-neuron communication are diverse, although regulated exocytosis has received the most attention but also caused the most debate. Similar to most of eukaryotic cells, astrocytes have a complex range of vesicular organelles which can undergo exocytosis as well as intricate molecular mechanisms that regulate this process. In this review, we focus on the components needed for regulated exocytosis to occur and summarise the knowledge about experimental evidence showing its presence in astrocytes.
Topics: Animals; Astrocytes; Calcium; Exocytosis; Humans; Models, Biological; Secretory Vesicles; Synaptic Vesicles
PubMed: 34572580
DOI: 10.3390/biom11091367 -
Frontiers in Immunology 2021Neutrophils are the most abundant innate immune cell with critical anti-microbial functions. Since the discovery of granulocytes at the end of the nineteenth century,... (Review)
Review
Neutrophils are the most abundant innate immune cell with critical anti-microbial functions. Since the discovery of granulocytes at the end of the nineteenth century, the cells have been given many names including phagocytes, polymorphonuclear neutrophils (PMN), granulocytic myeloid derived suppressor cells (G-MDSC), low density neutrophils (LDN) and tumor associated neutrophils (TANS). This lack of standardized nomenclature for neutrophils suggest that biologically distinct populations of neutrophils exist, particularly in disease, when in fact these may simply be a manifestation of the plasticity of the neutrophil as opposed to unique populations. In this review, we profile the surface markers and granule expression of each stage of granulopoiesis to offer insight into how each stage of maturity may be identified. We also highlight the remarkable surface marker expression profiles between the supposed neutrophil populations.
Topics: Gene Expression Regulation; Humans; Myeloid-Derived Suppressor Cells; Neutrophils; Secretory Vesicles; Terminology as Topic
PubMed: 33936029
DOI: 10.3389/fimmu.2021.602963