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Brain Research Bulletin Nov 2022Three different barriers are formed between the cerebrovascular and the brain parenchyma: the blood-brain barrier (BBB), the blood-cerebrospinal fluid barrier (BCSFB),... (Review)
Review
Three different barriers are formed between the cerebrovascular and the brain parenchyma: the blood-brain barrier (BBB), the blood-cerebrospinal fluid barrier (BCSFB), and the cerebrospinal fluid-brain barrier (CBB). The BBB is the main regulator of blood and central nervous system (CNS) material exchange. The semipermeable nature of the BBB limits the passage of larger molecules and hydrophilic small molecules, Food and Drug Administration (FDA)-approved drugs for the CNS have been generally limited to lipid-soluble small molecules. Although the complexity of the BBB affects CNS drug delivery, understanding the composition and function of the BBB can provide a platform for the development of new methods for CNS drug delivery. This review summarizes the classification of the brain barrier, the composition and role of the basic structures of the BBB, and the transport, barrier, and destruction mechanisms of the BBB; discusses the advantages and disadvantages of different drug delivery methods and prospects for future drug delivery strategies.
Topics: Brain; Blood-Brain Barrier; Drug Delivery Systems; Central Nervous System; Biological Transport
PubMed: 36162603
DOI: 10.1016/j.brainresbull.2022.09.017 -
American Journal of Physiology. Lung... Nov 2017Maintenance of normal epithelial ion and water transport in the lungs includes providing a thin layer of surface liquid that coats the conducting airways. This airway... (Review)
Review
Maintenance of normal epithelial ion and water transport in the lungs includes providing a thin layer of surface liquid that coats the conducting airways. This airway surface liquid is critical for normal lung function in a number of ways but, perhaps most importantly, is required for normal mucociliary clearance and bacterial removal. Preservation of the appropriate level of hydration, pH, and viscosity for the airway surface liquid requires the proper regulation and function of a battery of different types of ion channels and transporters. Here we discuss how alterations in ion channel/transporter function often lead to lung pathologies.
Topics: Animals; Biological Transport; Humans; Ion Channels; Ion Transport; Lung; Mucociliary Clearance; Respiratory Mucosa
PubMed: 29025712
DOI: 10.1152/ajplung.00285.2017 -
Cold Spring Harbor Perspectives in... Oct 2014The membrane-trafficking system underpins cellular trafficking of material in eukaryotes and its evolution would have been a watershed in eukaryogenesis. Evolutionary... (Review)
Review
The membrane-trafficking system underpins cellular trafficking of material in eukaryotes and its evolution would have been a watershed in eukaryogenesis. Evolutionary cell biological studies have been unraveling the history of proteins responsible for vesicle transport and organelle identity revealing both highly conserved components and lineage-specific innovations. Recently, endomembrane components with a broad, but patchy, distribution have been observed as well, pieces that are missing from our cell biological and evolutionary models of membrane trafficking. These data together allow for new insights into the history and forces that shape the evolution of this critical cell biological system.
Topics: Biological Transport; Cell Membrane; Eukaryotic Cells; Evolution, Molecular; Membrane Transport Proteins; Models, Biological
PubMed: 25274701
DOI: 10.1101/cshperspect.a016048 -
Cold Spring Harbor Perspectives in... Mar 2017Directional fluid flow is an essential process for embryo development as well as for organ and organism homeostasis. Here, we review the diverse structure of various... (Review)
Review
Directional fluid flow is an essential process for embryo development as well as for organ and organism homeostasis. Here, we review the diverse structure of various organ-blood barriers, the driving forces, transporters, and polarity mechanisms that regulate fluid transport across them, focusing on kidney-, eye-, and brain-blood barriers. We end by discussing how cross talk between barrier epithelial and endothelial cells, perivascular cells, and basement membrane signaling contribute to generate and maintain organ-blood barriers.
Topics: Biological Transport; Cell Polarity; Endothelial Cells; Extracellular Matrix; Homeostasis; Humans; Signal Transduction
PubMed: 28003183
DOI: 10.1101/cshperspect.a027847 -
The Journal of Physiology Sep 2015After providing a personal description of the convoluted path leading 25 years ago to the molecular identification of the Torpedo Cl(-) channel ClC-0 and the discovery... (Review)
Review
After providing a personal description of the convoluted path leading 25 years ago to the molecular identification of the Torpedo Cl(-) channel ClC-0 and the discovery of the CLC gene family, I succinctly describe the general structural and functional features of these ion transporters before giving a short overview of mammalian CLCs. These can be categorized into plasma membrane Cl(-) channels and vesicular Cl(-) /H(+) -exchangers. They are involved in the regulation of membrane excitability, transepithelial transport, extracellular ion homeostasis, endocytosis and lysosomal function. Diseases caused by CLC dysfunction include myotonia, neurodegeneration, deafness, blindness, leukodystrophy, male infertility, renal salt loss, kidney stones and osteopetrosis, revealing a surprisingly broad spectrum of biological roles for chloride transport that was unsuspected when I set out to clone the first voltage-gated chloride channel.
Topics: Animals; Biological Transport; Carrier Proteins; Cell Membrane; Chloride Channels; Chlorides; Cloning, Molecular; Humans; Ion Transport
PubMed: 25590607
DOI: 10.1113/JP270043 -
Trends in Plant Science Jan 2017Control of cell volume and osmolarity is central to cellular homeostasis in all eukaryotes. It lies at the heart of the century-old problem of how plants regulate... (Review)
Review
Control of cell volume and osmolarity is central to cellular homeostasis in all eukaryotes. It lies at the heart of the century-old problem of how plants regulate turgor, mineral and water transport. Plants use strongly electrogenic H-ATPases, and the substantial membrane voltages they foster, to drive solute accumulation and generate turgor pressure for cell expansion. Vesicle traffic adds membrane surface and contributes to wall remodelling as the cell grows. Although a balance between vesicle traffic and ion transport is essential for cell turgor and volume control, the mechanisms coordinating these processes have remained obscure. Recent discoveries have now uncovered interactions between conserved subsets of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins that drive the final steps in secretory vesicle traffic and ion channels that mediate in inorganic solute uptake. These findings establish the core of molecular links, previously unanticipated, that coordinate cellular homeostasis and cell expansion.
Topics: Biological Transport; Plant Physiological Phenomena; Plant Proteins; Potassium Channels; Protein Binding; SNARE Proteins
PubMed: 27818003
DOI: 10.1016/j.tplants.2016.10.006 -
Traffic (Copenhagen, Denmark) Dec 2005Small GTPases of the Rab family control timing of vesicle fusion. Fusion of two vesicles can only occur when they have been brought into close contact. Transport by... (Review)
Review
Small GTPases of the Rab family control timing of vesicle fusion. Fusion of two vesicles can only occur when they have been brought into close contact. Transport by microtubule- or actin-based motor proteins will facilitate this process in vivo. Ideally, transport and vesicle fusion are linked activities. Active, GTP-bound Rab proteins dock on specific compartments and are therefore perfect candidates to control transport of the different compartments. Recently, a number of Rab proteins were identified that control motor protein recruitment to their specific target membranes. By cycling through inactive and active states, Rab proteins are able to control motor protein-mediated transport and subsequent fusion of intracellular structures in both spatial and timed manners.
Topics: Animals; Biological Transport, Active; Cytoplasmic Vesicles; Humans; Membrane Fusion; Protein Transport; rab GTP-Binding Proteins
PubMed: 16262719
DOI: 10.1111/j.1600-0854.2005.00336.x -
Physiological Research Apr 2020Transcellular trafficking in which various molecules are transported across the interior of a cell, is commonly classified as transcytosis. However, historically this... (Review)
Review
Transcellular trafficking in which various molecules are transported across the interior of a cell, is commonly classified as transcytosis. However, historically this term has been used synonymously with transudation. In both cases transcellular trafficking starts with the internalization of proteins or other compounds on the basal or basolateral side of a cell and continues by their transport across the interior to the apical pole (or vice versa) where they are subsequently released. This allows a cell to release products which are synthesized elsewhere. Here, we discuss the common features of both transcytosis and transudation, and that which differentiates them. It appears that transcytosis and transudation are identical in terms of vesicular import and endosomal sorting of cargo, but completely differ in the re-secretion process. Specialized epithelial cells re-release substantial quantities of the endocytosed material, and often also a great variety. Some recent studies indicate that this is achieved by non-canonical apocrine secretion rather than by the regular vesicular mechanism of exocytosis, and takes place only on the apical pole. This massive re-release of endocytosed proteins, and potentially other compounds via the apocrine mechanism should be considered as transudation, distinct from transcytosis.
Topics: Animals; Apocrine Glands; Biological Transport; Endocytosis; Exocytosis; Humans; Transcytosis
PubMed: 32199009
DOI: 10.33549/physiolres.934229 -
Annual Review of Physiology 2016Exosomes are nanosized membrane particles that are secreted by cells that transmit information from cell to cell. The information within exosomes prominently includes... (Review)
Review
Exosomes are nanosized membrane particles that are secreted by cells that transmit information from cell to cell. The information within exosomes prominently includes their protein and RNA payloads. Exosomal microRNAs in particular can potently and fundamentally alter the transcriptome of recipient cells. Here we summarize what is known about exosome biogenesis, content, and transmission, with a focus on cardiovascular physiology and pathophysiology. We also highlight some of the questions currently under active investigation regarding these extracellular membrane vesicles and their potential in diagnostic and therapeutic applications.
Topics: Animals; Biological Transport; Cardiovascular Physiological Phenomena; Exosomes; Humans; MicroRNAs
PubMed: 26667071
DOI: 10.1146/annurev-physiol-021115-104929 -
Cytoskeleton (Hoboken, N.J.) Mar 2020The highly polarized, typically very long, and nonmitotic nature of neurons present them with unique challenges in the maintenance of their homeostasis. This... (Review)
Review
The highly polarized, typically very long, and nonmitotic nature of neurons present them with unique challenges in the maintenance of their homeostasis. This architectural complexity serves a rich and tightly controlled set of functions that enables their fast communication with neighboring cells and endows them with exquisite plasticity. The submembrane neuronal cytoskeleton occupies a pivotal position in orchestrating the structural patterning that determines local and long-range subcellular specialization, membrane dynamics, and a wide range of signaling events. At its center is the partnership between ankyrins and spectrins, which self-assemble with both remarkable long-range regularity and micro- and nanoscale specificity to precisely position and stabilize cell adhesion molecules, membrane transporters, ion channels, and other cytoskeletal proteins. To accomplish these generally conserved, but often functionally divergent and spatially diverse, roles these partners use a combinatorial program of a couple of dozens interacting family members, whose code is not fully unraveled. In a departure from their scaffolding roles, ankyrins and spectrins also enable the delivery of material to the plasma membrane by facilitating intracellular transport. Thus, it is unsurprising that deficits in ankyrins and spectrins underlie several neurodevelopmental, neurodegenerative, and psychiatric disorders. Here, I summarize key aspects of the biology of spectrins and ankyrins in the mammalian neuron and provide a snapshot of the latest advances in decoding their roles in the nervous system.
Topics: Ankyrins; Biological Transport; Neurons; Spectrin
PubMed: 32034889
DOI: 10.1002/cm.21602