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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 -
Journal of Neurochemistry Jun 2016Regulated exocytosis is a multistage process involving a merger between the vesicle and the plasma membrane, leading to the formation of a fusion pore, a channel,... (Review)
Review
Regulated exocytosis is a multistage process involving a merger between the vesicle and the plasma membrane, leading to the formation of a fusion pore, a channel, through which secretions are released from the vesicle to the cell exterior. A stimulus may influence the pore by either dilating it completely (full-fusion exocytosis) or mediating a reversible closure (transient exocytosis). In neurons, these transitions are short-lived and not accessible for experimentation. However, in some neuroendocrine cells and astrocytes, initial fusion pores may reopen several hundred times, indicating their stability. Frequently, these pores are too narrow to pass luminal molecules to the extracellular space (unproductive exocytosis), but their diameter can dilate upon stimulation. To explain the stability of the initial narrow fusion pores, anisotropic membrane constituents with a non-axisymmetric shape were proposed to accumulate in the fusion pore membrane. Although the nature of these is unclear, they may consist of lipids and proteins, including SNAREs, which may facilitate and regulate the pre- and post-fusional stages of exocytosis. This review highlights models and experimental studies revealing mechanisms of fusion pore stabilization in a narrow, release unproductive state. The fusion pore is a channel that forms when the vesicle and the plasma membranes merge, and mediates the release of secretions from the vesicle lumen to the cell exterior. Frequently, these pores are too narrow to pass molecules to the extracellular space. Anisotropic membrane constituents with a non-axisymmetric shape were proposed to accumulate in the fusion pore membrane. This article is part of a mini review series on Chromaffin cells (ISCCB Meeting, 2015).
Topics: Animals; Calcium; Cell Membrane; Exocytosis; Humans; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; Membrane Fusion; Secretory Vesicles
PubMed: 26841731
DOI: 10.1111/jnc.13561 -
ELife Nov 2023A receptor protein called TGN46 has an important role in sorting secretory proteins into vesicles going to different destinations inside cells.
A receptor protein called TGN46 has an important role in sorting secretory proteins into vesicles going to different destinations inside cells.
Topics: trans-Golgi Network; Proteins; Protein Transport; Golgi Apparatus; Secretory Vesicles
PubMed: 37997893
DOI: 10.7554/eLife.93490 -
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 -
Journal of Cell Science Apr 2017Real-time imaging of regulated exocytosis in secreting organs can provide unprecedented temporal and spatial detail. Here, we highlight recent advances in 3D time-lapse... (Review)
Review
Real-time imaging of regulated exocytosis in secreting organs can provide unprecedented temporal and spatial detail. Here, we highlight recent advances in 3D time-lapse imaging in salivary glands at single-granule resolution. Using fluorescently labeled proteins expressed in the fly, it is now possible to image the dynamics of vesicle biogenesis and the cytoskeletal factors involved in secretion. 3D imaging over time allows one to visualize and define the temporal sequence of events, including clearance of cortical actin, fusion pore formation, mixing of the vesicular and plasma membranes and recruitment of components of the cytoskeleton. We will also discuss the genetic tools available in the fly that allow one to interrogate the essential factors involved in secretory vesicle formation, cargo secretion and the ultimate integration of the vesicular and plasma membranes. We argue that the combination of high-resolution real-time imaging and powerful genetics provides a platform to investigate the role of any factor in regulated secretion.
Topics: Animals; Cytoskeleton; Drosophila; Exocytosis; Humans; Imaging, Three-Dimensional; Membrane Fusion; Microscopy, Fluorescence; Molecular Biology; Salivary Glands; Secretory Vesicles; Time-Lapse Imaging
PubMed: 28302911
DOI: 10.1242/jcs.193425 -
Cells Jun 2020Cellular secretion depends on exocytosis of secretory vesicles and discharge of vesicle contents. Actin and myosin are essential for pre-fusion and post-fusion stages of... (Review)
Review
Cellular secretion depends on exocytosis of secretory vesicles and discharge of vesicle contents. Actin and myosin are essential for pre-fusion and post-fusion stages of exocytosis. Secretory vesicles depend on actin for transport to and attachment at the cell cortex during the pre-fusion phase. Actin coats on fused vesicles contribute to stabilization of large vesicles, active vesicle contraction and/or retrieval of excess membrane during the post-fusion phase. Myosin molecular motors complement the role of actin. Myosin V is required for vesicle trafficking and attachment to cortical actin. Myosin I and II members engage in local remodeling of cortical actin to allow vesicles to get access to the plasma membrane for membrane fusion. Myosins stabilize open fusion pores and contribute to anchoring and contraction of actin coats to facilitate vesicle content release. Actin and myosin function in secretion is regulated by a plethora of interacting regulatory lipids and proteins. Some of these processes have been first described in non-neuronal cells and reflect adaptations to exocytosis of large secretory vesicles and/or secretion of bulky vesicle cargoes. Here we collate the current knowledge and highlight the role of actomyosin during distinct phases of exocytosis in an attempt to identify unifying molecular mechanisms in non-neuronal secretory cells.
Topics: Actin Cytoskeleton; Actins; Animals; Exocytosis; Humans; Membrane Fusion; Myosins; Secretory Vesicles
PubMed: 32545391
DOI: 10.3390/cells9061455 -
Microbiology Spectrum Apr 2015Proteinaceous components of the biofilm matrix include secreted extracellular proteins, cell surface adhesins, and protein subunits of cell appendages such as flagella... (Review)
Review
Proteinaceous components of the biofilm matrix include secreted extracellular proteins, cell surface adhesins, and protein subunits of cell appendages such as flagella and pili. Biofilm matrix proteins play diverse roles in biofilm formation and dissolution. They are involved in attaching cells to surfaces, stabilizing the biofilm matrix via interactions with exopolysaccharide and nucleic acid components, developing three-dimensional biofilm architectures, and dissolving biofilm matrix via enzymatic degradation of polysaccharides, proteins, and nucleic acids. In this article, we will review functions of matrix proteins in a selected set of microorganisms, studies of the matrix proteomes of Vibrio cholerae and Pseudomonas aeruginosa, and roles of outer membrane vesicles and of nucleoid-binding proteins in biofilm formation.
Topics: Bacterial Proteins; Biofilms; Extracellular Matrix; Pseudomonas aeruginosa; Secretory Vesicles; Vibrio cholerae
PubMed: 26104709
DOI: 10.1128/microbiolspec.MB-0004-2014 -
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 -
Frontiers in Immunology 2020is the causative agent of a severe pneumonia called Legionnaires' disease. The environmental bacterium replicates in free-living amoebae as well as in lung macrophages... (Review)
Review
is the causative agent of a severe pneumonia called Legionnaires' disease. The environmental bacterium replicates in free-living amoebae as well as in lung macrophages in a distinct compartment, the -containing vacuole (LCV). The LCV communicates with a number of cellular vesicle trafficking pathways and is formed by a plethora of secreted bacterial effector proteins, which target host cell proteins and lipids. Phosphoinositide (PI) lipids are pivotal determinants of organelle identity, membrane dynamics and vesicle trafficking. Accordingly, eukaryotic cells tightly regulate the production, turnover, interconversion, and localization of PI lipids. modulates the PI pattern in infected cells for its own benefit by (i) recruiting PI-decorated vesicles, (ii) producing effectors acting as PI interactors, phosphatases, kinases or phospholipases, and (iii) subverting host PI metabolizing enzymes. The PI conversion from PtdIns(3) to PtdIns(4) represents a decisive step during LCV maturation. In this review, we summarize recent progress on elucidating the strategies, by which subverts host PI lipids to promote LCV formation and intracellular replication.
Topics: Bacterial Proteins; Cell Membrane; Endoplasmic Reticulum; Host-Pathogen Interactions; Humans; Legionella pneumophila; Legionnaires' Disease; Macrophages; Phosphatidylinositols; Secretory Vesicles; Transport Vesicles; Vacuoles
PubMed: 32117224
DOI: 10.3389/fimmu.2020.00025 -
Annals of the American Thoracic Society Nov 2018Exocytosis of secreted mucins is the final step in their intracellular processing, resulting in their release into the airway lumen to interact with water and ions to... (Review)
Review
Exocytosis of secreted mucins is the final step in their intracellular processing, resulting in their release into the airway lumen to interact with water and ions to form mucus. Mucins are secreted at a low baseline rate and a high stimulated rate, and both rates are regulated by second messengers acting on components of the exocytic machinery. The principal physiologic function of the low baseline rate is to support steady-state mucociliary clearance of inhaled particles and pathogens that enter the airways during normal breathing. Even in the setting of mucin hyperproduction, baseline secretion generally does not induce mucus occlusion. The principal physiologic function of the high stimulated rate of secretion from both submucosal glands and surface goblet cells in proximal airways appears to be to sweep away larger particles, whereas in distal airways it appears to act in concert with mucin hyperproduction to induce mucus occlusion to trap migrating helminths. Pathophysiologically, stimulated mucin secretion in the setting of mucin hyperproduction from allergic or other types of airway inflammation in the absence of helminth infection causes airflow obstruction and infection. Molecular components of the mucin exocytic machinery are increasingly being identified, and surprisingly, many components are not shared between baseline and stimulated machines. The physiologic significance of the presence of two distinct molecular machines is not yet known, such as whether these interact selectively with secretory granules of different sizes or contents. A full understanding of the mechanism and regulation of airway mucin secretion will provide further insight into pathophysiologic processes and may identify therapeutic strategies to alleviate obstructive airway diseases.
Topics: Exocytosis; Humans; Lung Diseases; Mucins; Mucociliary Clearance; Mucus; Respiratory Mucosa; Secretory Vesicles
PubMed: 30431339
DOI: 10.1513/AnnalsATS.201806-371AW