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Journal of the American Society of... Oct 2022
Topics: Glucose; Biological Transport
PubMed: 36630519
DOI: 10.1681/ASN.2022070841 -
Physiological Reviews Jan 2021Phosphate is an essential nutrient for life and is a critical component of bone formation, a major signaling molecule, and structural component of cell walls. Phosphate... (Review)
Review
Phosphate is an essential nutrient for life and is a critical component of bone formation, a major signaling molecule, and structural component of cell walls. Phosphate is also a component of high-energy compounds (i.e., AMP, ADP, and ATP) and essential for nucleic acid helical structure (i.e., RNA and DNA). Phosphate plays a central role in the process of mineralization, normal serum levels being associated with appropriate bone mineralization, while high and low serum levels are associated with soft tissue calcification. The serum concentration of phosphate and the total body content of phosphate are highly regulated, a process that is accomplished by the coordinated effort of two families of sodium-dependent transporter proteins. The three isoforms of the SLC34 family (SLC34A1-A3) show very restricted tissue expression and regulate intestinal absorption and renal excretion of phosphate. SLC34A2 also regulates the phosphate concentration in multiple lumen fluids including milk, saliva, pancreatic fluid, and surfactant. Both isoforms of the SLC20 family exhibit ubiquitous expression (with some variation as to which one or both are expressed), are regulated by ambient phosphate, and likely serve the phosphate needs of the individual cell. These proteins exhibit similarities to phosphate transporters in nonmammalian organisms. The proteins are nonredundant as mutations in each yield unique clinical presentations. Further research is essential to understand the function, regulation, and coordination of the various phosphate transporters, both the ones described in this review and the phosphate transporters involved in intracellular transport.
Topics: Animals; Biological Transport; Epithelium; Homeostasis; Humans; Phosphates; Sodium-Phosphate Cotransporter Proteins
PubMed: 32353243
DOI: 10.1152/physrev.00008.2019 -
ASN Neuro 2022Vesicles mediate the trafficking of membranes/proteins in the endocytic and secretory pathways. These pathways are regulated by small GTPases of the Rab family. Rab... (Review)
Review
Vesicles mediate the trafficking of membranes/proteins in the endocytic and secretory pathways. These pathways are regulated by small GTPases of the Rab family. Rab proteins belong to the Ras superfamily of GTPases, which are significantly involved in various intracellular trafficking and signaling processes in the nervous system. Rab11 is known to play a key role especially in recycling many proteins, including receptors important for signal transduction and preservation of functional activities of nerve cells. Rab11 activity is controlled by GEFs (guanine exchange factors) and GAPs (GTPase activating proteins), which regulate its function through modulating GTP/GDP exchange and the intrinsic GTPase activity, respectively. Rab11 is involved in the transport of several growth factor molecules important for the development and repair of neurons. Overexpression of Rab11 has been shown to significantly enhance vesicle trafficking. On the other hand, a reduced expression of Rab11 was observed in several neurodegenerative diseases. Current evidence appears to support the notion that Rab11 and its cognate proteins may be potential targets for therapeutic intervention. In this review, we briefly discuss the function of Rab11 and its related interaction partners in intracellular pathways that may be involved in neurodegenerative processes.
Topics: Humans; Membrane Proteins; Neurodegenerative Diseases; Neurons; Signal Transduction; Biological Transport
PubMed: 36464817
DOI: 10.1177/17590914221142360 -
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 -
Function (Oxford, England) 2021
Topics: Glucose; Biological Transport; Biological Transport, Active
PubMed: 33511351
DOI: 10.1093/function/zqaa047 -
FEBS Letters Jul 2010The polytopic transmembrane protein, Niemann-Pick C1-Like 1 (NPC1L1), is enriched in the apical membrane of small intestine absorptive enterocytes where it mediates... (Review)
Review
The polytopic transmembrane protein, Niemann-Pick C1-Like 1 (NPC1L1), is enriched in the apical membrane of small intestine absorptive enterocytes where it mediates extracellular sterol transport across the brush border membrane. It is essential for intestinal sterol absorption and is the molecular target of ezetimibe, a potent cholesterol absorption inhibitor that lowers blood cholesterol in humans. NPC1L1 is also highly expressed in human liver. The hepatic function of NPC1L1 may be to limit excessive biliary cholesterol loss. NPC1L1-dependent sterol uptake seems to be a clathrin-mediated endocytic process and is regulated by cellular cholesterol content. Recently, NPC1L1 inhibition has been shown to have beneficial effects on components of the metabolic syndrome, such as obesity, insulin resistance, and fatty liver, in addition to atherosclerosis.
Topics: Animals; Azetidines; Biological Transport; Cholesterol; Ezetimibe; Humans; Membrane Proteins; Membrane Transport Proteins; Substrate Specificity
PubMed: 20307540
DOI: 10.1016/j.febslet.2010.03.030 -
International Journal of Molecular... Feb 2022The organic cation transporter 1 (OCT1, ) transports a large number of structurally diverse endogenous and exogenous substrates. There are numerous known competitive and...
The organic cation transporter 1 (OCT1, ) transports a large number of structurally diverse endogenous and exogenous substrates. There are numerous known competitive and non-competitive inhibitors of OCT1, but there are no studies systematically analyzing the relationship between transport, stimulation, and inhibition. Here, we tested in vitro OCT1 inhibition by OCT1 substrates and transport of OCT1 inhibitors under uniform analytical conditions. Beyond inhibition testing with two model substrates, we tested nine additional OCT1 substrates for their mutual inhibition. Inhibition of ASP uptake by most OCT1 substrates was weak. The model substrate sumatriptan, with its moderately stronger inhibitability, was used to confirm this. Interestingly, OCT1 substrates exhibiting stronger OCT1 inhibition were mainly biaromatic β-agonistic drugs, such as dobutamine, fenoterol, ractopamine and ritodrine. Biaromatic organic cations were both, strong inhibitors and good substrates, but many OCT1 substrates showed little pairwise inhibition. Surprisingly, sumatriptan did significantly enhance dobutamine uptake. This effect was concentration dependent and additional experiments indicated that efflux inhibition may be one of the underlying mechanisms. Our data suggests, that OCT1 substrates are mainly weak OCT1 inhibitors and among those inhibiting well, noncompetitive inhibition could be responsible. Weak competitive inhibition confirms that OCT1 inhibition screenings poorly predict OCT1 substrates. Additionally, we showed that the OCT1 substrate sumatriptan can enhance uptake of some other OCT1 substrates. OCT1 transport stimulation was already observed earlier but is still poorly understood. Low OCT1 uptake inhibition and strong OCT1 efflux inhibition could be mechanisms exploitable for enhancing transport.
Topics: Biological Transport; Cell Line; HEK293 Cells; Humans; Octamer Transcription Factor-1
PubMed: 35216120
DOI: 10.3390/ijms23042007 -
The Plant Cell Jan 2015Auxin participates in a multitude of developmental processes, as well as responses to environmental cues. Compared with other plant hormones, auxin exhibits a unique... (Review)
Review
Auxin participates in a multitude of developmental processes, as well as responses to environmental cues. Compared with other plant hormones, auxin exhibits a unique property, as it undergoes directional, cell-to-cell transport facilitated by plasma membrane-localized transport proteins. Among them, a prominent role has been ascribed to the PIN family of auxin efflux facilitators. PIN proteins direct polar auxin transport on account of their asymmetric subcellular localizations. In this review, we provide an overview of the multiple developmental roles of PIN proteins, including the atypical endoplasmic reticulum-localized members of the family, and look at the family from an evolutionary perspective. Next, we cover the cell biological and molecular aspects of PIN function, in particular the establishment of their polar subcellular localization. Hormonal and environmental inputs into the regulation of PIN action are summarized as well.
Topics: Biological Transport; Gene Expression Regulation, Plant; Indoleacetic Acids; Membrane Transport Proteins
PubMed: 25604445
DOI: 10.1105/tpc.114.134874 -
Current Biology : CB May 2020The membrane-trafficking system is a defining facet of eukaryotic cells. The best-known organelles and major protein families of this system are largely conserved across... (Review)
Review
The membrane-trafficking system is a defining facet of eukaryotic cells. The best-known organelles and major protein families of this system are largely conserved across the vast diversity of eukaryotes, implying both ancient organization and functional unity. Nonetheless, intriguing variation exists that speaks to the evolutionary forces that have shaped the endomembrane system in eukaryotes and highlights ways in which membrane trafficking in protists differs from that in our well-understood models of mammalian and yeast cells. Both parasites and free-living protists possess specialized trafficking organelles, some lineage specific, others more widely distributed - the evolution and function of these organelles begs exploration. Novel members of protein families are present across eukaryotes but have been lost in humans. These proteins may well hold clues to understanding differences in cellular function in organisms that are of pressing importance for planetary health.
Topics: Animals; Biodiversity; Biological Evolution; Biological Transport; Cell Membrane; Eukaryota
PubMed: 32428497
DOI: 10.1016/j.cub.2020.03.068 -
Developmental Cell Oct 2019Spatiotemporal organization during development has frequently been proposed to be explainable by reaction-transport models, where biochemical reactions couple to... (Review)
Review
Spatiotemporal organization during development has frequently been proposed to be explainable by reaction-transport models, where biochemical reactions couple to physical motion. However, whereas genetic tools allow causality of molecular players to be dissected via perturbation experiments, the functional role of physical transport processes, such as diffusion and cytoplasmic streaming, frequently remains untestable. This Perspective explores the challenges of validating reaction-transport hypotheses and highlights new opportunities provided by perturbation approaches that specifically target physical transport mechanisms. Using these methods, experimental physics may begin to catch up with molecular biology and find ways to test roles of diffusion and flows in development.
Topics: Animals; Biological Transport; Cell Physiological Phenomena; Cytoplasmic Streaming; Diffusion; Humans; Models, Biological; Motion
PubMed: 31639366
DOI: 10.1016/j.devcel.2019.10.002