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Current Biology : CB Apr 2018A fundamental hallmark of eukaryotic cells is their compartmentalization into functionally distinct organelles, including those of the secretory and endocytic pathways.... (Review)
Review
A fundamental hallmark of eukaryotic cells is their compartmentalization into functionally distinct organelles, including those of the secretory and endocytic pathways. Transport of cargo between these compartments and to/from the cell surface is mediated by membrane-bound vesicles and tubules. Delivery of cargo is facilitated by SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor)-mediated membrane fusion of vesicles with their target compartments. Vesicles contain a variety of cargos, including lipids, membrane proteins, signaling molecules, biosynthetic and hydrolytic enzymes, and the trafficking machinery itself. Proper function of membrane trafficking is required for cellular growth, division, movement, and cell-cell communication. Defects in these processes have been implicated in a variety of human diseases, such as cancer, diabetes, neurodegenerative disorders, ciliopathies, and infections. The elucidation of the mechanisms of SNARE assembly and disassembly is key to understanding how membrane fusion is regulated throughout eukaryotes. Here, we introduce the SNARE proteins, their structures and functions in eukaryotic cells, and discuss recent breakthroughs in elucidating the regulation of SNARE assembly and disassembly through the use of high-resolution structural biology and biophysical techniques.
Topics: Animals; Biological Transport; Cell Membrane; Humans; Membrane Fusion; Protein Binding; Protein Transport; SNARE Proteins
PubMed: 29689222
DOI: 10.1016/j.cub.2018.01.005 -
International Journal of Molecular... Mar 2021Membranes plays enormous role in our life [...].
Membranes plays enormous role in our life [...].
Topics: Animals; Biological Transport; Cell Membrane; Ions; Membrane Proteins; Membranes, Artificial; Nanoparticles
PubMed: 33808070
DOI: 10.3390/ijms22073556 -
Med (New York, N.Y.) Dec 2022The near impermeability of the blood-brain barrier (BBB) and the unique neuroimmune environment of the CNS prevents the effective use of antibodies in neurological...
BACKGROUND
The near impermeability of the blood-brain barrier (BBB) and the unique neuroimmune environment of the CNS prevents the effective use of antibodies in neurological diseases. Delivery of biotherapeutics to the brain can be enabled through receptor-mediated transcytosis via proteins such as the transferrin receptor, although limitations such as the ability to use Fc-mediated effector function to clear pathogenic targets can introduce safety liabilities. Hence, novel delivery approaches with alternative clearance mechanisms are warranted.
METHODS
Binders that optimized transport across the BBB, known as transcytosis-enabling modules (TEMs), were identified using a combination of antibody discovery techniques and pharmacokinetic analyses. Functional activity of TEMs were subsequently evaluated by imaging for the ability of myeloid cells to phagocytose target proteins and cells.
FINDINGS
We demonstrated significantly enhanced brain exposure of therapeutic antibodies using optimal transferrin receptor or CD98 TEMs. We found that these modules also mediated efficient clearance of tau aggregates and HER2+ tumor cells via a non-classical phagocytosis mechanism through direct engagement of myeloid cells. This mode of clearance potentially avoids the known drawbacks of FcγR-mediated antibody mechanisms in the brain such as the neurotoxic release of proinflammatory cytokines and immune cell exhaustion.
CONCLUSIONS
Our study reports a new brain delivery platform that harnesses receptor-mediated transcytosis to maximize brain uptake and uses a non-classical phagocytosis mechanism to efficiently clear pathologic proteins and cells. We believe these findings will transform therapeutic approaches to treat CNS diseases.
FUNDING
This research was funded by Janssen, Pharmaceutical Companies of Johnson & Johnson.
Topics: Blood-Brain Barrier; Transcytosis; Receptors, Transferrin; Biological Transport; Antibodies
PubMed: 36257298
DOI: 10.1016/j.medj.2022.09.007 -
Plant Physiology Feb 2022
Topics: Biochemical Phenomena; Biological Transport; Cell Membrane; Membrane Transport Proteins; Plant Physiological Phenomena; Signal Transduction
PubMed: 34908141
DOI: 10.1093/plphys/kiab585 -
International Journal of Molecular... Mar 2023The main component of blood and lymphatic vessels is the endothelium covering their luminal surface. It plays a significant role in many cardiovascular diseases.... (Review)
Review
The main component of blood and lymphatic vessels is the endothelium covering their luminal surface. It plays a significant role in many cardiovascular diseases. Tremendous progress has been made in deciphering of molecular mechanisms involved into intracellular transport. However, molecular machines are mostly characterized in vitro. It is important to adapt this knowledge to the situation existing in tissues and organs. Moreover, contradictions have accumulated within the field related to the function of endothelial cells (ECs) and their trans-endothelial pathways. This has induced necessity for the re-evaluation of several mechanisms related to the function of vascular ECs and intracellular transport and transcytosis there. Here, we analyze available data related to intracellular transport within ECs and re-examine several hypotheses about the role of different mechanisms in transcytosis across ECs. We propose a new classification of vascular endothelium and hypotheses related to the functional role of caveolae and mechanisms of lipid transport through ECs.
Topics: Endothelial Cells; Biological Transport; Transcytosis; Caveolae; Intracellular Membranes; Endothelium, Vascular
PubMed: 36982865
DOI: 10.3390/ijms24065791 -
World Journal of Gastroenterology Sep 2007The liver plays a central role in iron metabolism. It is the major storage site for iron and also expresses a complex range of molecules which are involved in iron... (Review)
Review
The liver plays a central role in iron metabolism. It is the major storage site for iron and also expresses a complex range of molecules which are involved in iron transport and regulation of iron homeostasis. An increasing number of genes associated with hepatic iron transport or regulation have been identified. These include transferrin receptors (TFR1 and 2), a ferrireductase (STEAP3), the transporters divalent metal transporter-1 (DMT1) and ferroportin (FPN) as well as the haemochromatosis protein, HFE and haemojuvelin (HJV), which are signalling molecules. Many of these genes also participate in iron regulatory pathways which focus on the hepatic peptide hepcidin. However, we are still only beginning to understand the complex interactions between liver iron transport and iron homeostasis. This review outlines our current knowledge of molecules of iron metabolism and their roles in iron transport and regulation of iron homeostasis.
Topics: Biological Transport; Homeostasis; Humans; Iron; Kupffer Cells; Liver
PubMed: 17729394
DOI: 10.3748/wjg.v13.i35.4725 -
Frontiers in Immunology 2021
Topics: Biological Transport; Cell Membrane; Exocytosis; Genetic Predisposition to Disease; Humans; Immunologic Deficiency Syndromes; Mutation; Neoplasms
PubMed: 34659271
DOI: 10.3389/fimmu.2021.769815 -
Plant Physiology Dec 2021Far from a homogeneous environment, biological membranes are highly structured with lipids and proteins segregating in domains of different sizes and dwell times. In... (Review)
Review
Far from a homogeneous environment, biological membranes are highly structured with lipids and proteins segregating in domains of different sizes and dwell times. In addition, membranes are highly dynamics especially in response to environmental stimuli. Understanding the impact of the nanoscale organization of membranes on cellular functions is an outstanding question. Plant channels and transporters are tightly regulated to ensure proper cell nutrition and signaling. Increasing evidence indicates that channel and transporter nano-organization within membranes plays an important role in these regulation mechanisms. Here, we review recent advances in the field of ion, water, but also hormone transport in plants, focusing on protein organization within plasma membrane nanodomains and its cellular and physiological impacts.
Topics: Biological Transport; Cell Membrane; Microscopy, Fluorescence; Plant Physiological Phenomena; Signal Transduction
PubMed: 35235669
DOI: 10.1093/plphys/kiab312 -
Trends in Plant Science Jun 2017Cytokinins are phytohormones essential for cytokinesis and many other physiological and developmental processes in planta. Long-distance transport and intercellular... (Review)
Review
Cytokinins are phytohormones essential for cytokinesis and many other physiological and developmental processes in planta. Long-distance transport and intercellular transport have been postulated. For these processes, the existence of cytokinin transporters has been suggested. Recently, a transporter loading the xylem (AtABCG14) and another for cellular import (AtPUP14) have been discovered. AtABCG14 participates in the xylem loading process of cytokinins and contributes to the positive regulation of shoot growth. The cellular importer AtPUP14 is required to suppress cytokinin signaling. A role of a transporter as stop signal is a new paradigm for a hormone transporter.
Topics: Arabidopsis; Arabidopsis Proteins; Biological Transport; Cytokinins; Membrane Transport Proteins; Signal Transduction
PubMed: 28372884
DOI: 10.1016/j.tplants.2017.03.003 -
Molecular Biology of the Cell Dec 2022In 1956, referring to the emerging application of electron microscopy to the study of eukaryotic cells, Keith R. Porter wrote, "For those of us who are fortunate to be...
In 1956, referring to the emerging application of electron microscopy to the study of eukaryotic cells, Keith R. Porter wrote, "For those of us who are fortunate to be part of this new development, these are days of great interest and opportunity." Those early days left us a rich legacy of knowledge on the internal organization of eukaryotic cells that provides a framework for current research on cell structure and function. In this vein, my long-time quest has been to understand how proteins and organelles travel through the cytoplasm to reach their respective destinations within the cell. This research has led us to elucidate various mechanisms of protein sorting and organelle transport and how defects in these mechanisms cause human disease.
Topics: Humans; Organelles; Microscopy, Electron; Biological Transport; Cytoplasm; Protein Transport
PubMed: 36399622
DOI: 10.1091/mbc.E22-08-0362