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Annual Review of Physiology

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2016: Annual Review of Physiology
Christina S Bartlett, Marie Jeansson, Susan E Quaggin
The glomerulus is a highly specialized microvascular bed that filters blood to form primary urinary filtrate. It contains four cell types: fenestrated endothelial cells, specialized vascular support cells termed podocytes, perivascular mesangial cells, and parietal epithelial cells. Glomerular cell-cell communication is critical for the development and maintenance of the glomerular filtration barrier. VEGF, ANGPT, EGF, SEMA3A, TGF-β, and CXCL12 signal in paracrine fashions between the podocytes, endothelium, and mesangium associated with the glomerular capillary bed to maintain filtration barrier function...
2016: Annual Review of Physiology
Juliette Hadchouel, David H Ellison, Gerardo Gamba
The discovery of four genes responsible for pseudohypoaldosteronism type II, or familial hyperkalemic hypertension, which features arterial hypertension with hyperkalemia and metabolic acidosis, unmasked a complex multiprotein system that regulates electrolyte transport in the distal nephron. Two of these genes encode the serine-threonine kinases WNK1 and WNK4. The other two genes [kelch-like 3 (KLHL3) and cullin 3 (CUL3)] form a RING-type E3-ubiquitin ligase complex that modulates WNK1 and WNK4 abundance. WNKs regulate the activity of the Na(+):Cl(-) cotransporter (NCC), the epithelial sodium channel (ENaC), the renal outer medullary potassium channel (ROMK), and other transport pathways...
2016: Annual Review of Physiology
Bruce E Herring, Roger A Nicoll
For more than 20 years, we have known that Ca(2+)/calmodulin-dependent protein kinase (CaMKII) activation is both necessary and sufficient for the induction of long-term potentiation (LTP). During this time, tremendous effort has been spent in attempting to understand how CaMKII activation gives rise to this phenomenon. Despite such efforts, there is much to be learned about the molecular mechanisms involved in LTP induction downstream of CaMKII activation. In this review, we highlight recent developments that have shaped our current thinking about the molecular mechanisms underlying LTP and discuss important questions that remain in the field...
2016: Annual Review of Physiology
Amy K Sutton, Martin G Myers, David P Olson
Although it has been known for more than a century that the brain controls overall energy balance and adiposity by regulating feeding behavior and energy expenditure, the roles for individual brain regions and neuronal subtypes were not fully understood until recently. This area of research is active, and as such our understanding of the central regulation of energy balance is continually being refined as new details emerge. Much of what we now know stems from the discoveries of leptin and the hypothalamic melanocortin system...
2016: Annual Review of Physiology
José Antonio Enríquez
Since the discovery of the existence of superassemblies between mitochondrial respiratory complexes, such superassemblies have been the object of a passionate debate. It is accepted that respiratory supercomplexes are structures that occur in vivo, although which superstructures are naturally occurring and what could be their functional role remain open questions. The main difficulty is to make compatible the existence of superassemblies with the corpus of data that drove the field to abandon the early understanding of the physical arrangement of the mitochondrial respiratory chain as a compact physical entity (the solid model)...
2016: Annual Review of Physiology
Jennifer C Jones, Shelly Rustagi, Peter J Dempsey
A disintegrin and metalloproteinases (ADAMs) are a family of cell surface proteases that regulate diverse cellular functions, including cell adhesion, migration, cellular signaling, and proteolysis. Proteolytically active ADAMs are responsible for ectodomain shedding of membrane-associated proteins. ADAMs rapidly modulate key cell signaling pathways in response to changes in the extracellular environment (e.g., inflammation) and play a central role in coordinating intercellular communication within the local microenvironment...
2016: Annual Review of Physiology
János Peti-Peterdi, Bellamkonda K Kishore, Jennifer L Pluznick
To maintain metabolic homeostasis, the body must be able to monitor the concentration of a large number of substances, including metabolites, in real time and to use that information to regulate the activities of different metabolic pathways. Such regulation is achieved by the presence of sensors, termed metabolite receptors, in various tissues and cells of the body, which in turn convey the information to appropriate regulatory or positive or negative feedback systems. In this review, we cover the unique roles of metabolite receptors in renal and vascular function...
2016: Annual Review of Physiology
Sadeesh K Ramakrishnan, Yatrik M Shah
The intestine is supported by a complex vascular system that undergoes dynamic and transient daily shifts in blood perfusion, depending on the metabolic state. Moreover, the intestinal villi have a steep oxygen gradient from the hypoxic epithelium adjacent to the anoxic lumen to the relative higher tissue oxygenation at the base of villi. Due to the daily changes in tissue oxygen levels in the intestine, the hypoxic transcription factors hypoxia-inducible factor (HIF)-1α and HIF-2α are essential in maintaining intestinal homeostasis...
2016: Annual Review of Physiology
Lena Pernas, Luca Scorrano
Permanent residency in the eukaryotic cell pressured the prokaryotic mitochondrial ancestor to strategize for intracellular living. Mitochondria are able to autonomously integrate and respond to cellular cues and demands by remodeling their morphology. These processes define mitochondrial dynamics and inextricably link the fate of the mitochondrion and that of the host eukaryote, as exemplified by the human diseases that result from mutations in mitochondrial dynamics proteins. In this review, we delineate the architecture of mitochondria and define the mechanisms by which they modify their shape...
2016: Annual Review of Physiology
Maria A Sacta, Yurii Chinenov, Inez Rogatsky
Glucocorticoid hormones (GC) regulate essential physiological functions including energy homeostasis, embryonic and postembryonic development, and the stress response. From the biomedical perspective, GC have garnered a tremendous amount of attention as highly potent anti-inflammatory and immunosuppressive medications indispensable in the clinic. GC signal through the GC receptor (GR), a ligand-dependent transcription factor whose structure, DNA binding, and the molecular partners that it employs to regulate transcription have been under intense investigation for decades...
2016: Annual Review of Physiology
Irina Petrache, Evgeny V Berdyshev
Following the discovery of ceramide as the central signaling and metabolic relay among sphingolipids, studies of its involvement in lung health and pathophysiology have exponentially increased. In this review, we highlight key studies in the context of recent progress in metabolomics and translational research methodologies. Evidence points toward an important role for the ceramide/sphingosine-1-phosphate rheostat in maintaining lung cell survival, vascular barrier function, and proper host response to airway microbial infections...
2016: Annual Review of Physiology
Lisa A Gunaydin, Anatol C Kreitzer
Circuit dysfunction models of psychiatric disease posit that pathological behavior results from abnormal patterns of electrical activity in specific cells and circuits in the brain. Many psychiatric disorders are associated with abnormal activity in the prefrontal cortex and in the basal ganglia, a set of subcortical nuclei implicated in cognitive and motor control. Here we discuss the role of the basal ganglia and connected prefrontal regions in the etiology and treatment of obsessive-compulsive disorder, anxiety, and depression, emphasizing mechanistic work in rodent behavioral models to dissect causal cortico-basal ganglia circuits underlying discrete behavioral symptom domains relevant to these complex disorders...
2016: Annual Review of Physiology
Ahmed Ibrahim, Eduardo Marbán
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...
2016: Annual Review of Physiology
Joel T Haas, Sven Francque, Bart Staels
Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders characterized by abnormal hepatic fat accumulation, inflammation, and hepatocyte dysfunction. Importantly, it is also closely linked to obesity and the metabolic syndrome. NAFLD predisposes susceptible individuals to cirrhosis, hepatocellular carcinoma, and cardiovascular disease. Although the precise signals remain poorly understood, NAFLD pathogenesis likely involves actions of the different hepatic cell types and multiple extrahepatic signals...
2016: Annual Review of Physiology
Ffolliott Martin Fisher, Eleftheria Maratos-Flier
Fibroblast growth factor 21 (FGF21) is a peptide hormone that is synthesized by several organs and regulates energy homeostasis. Excitement surrounding this relatively recently identified hormone is based on the documented metabolic beneficial effects of FGF21, which include weight loss and improved glycemia. The biology of FGF21 is intrinsically complicated owing to its diverse metabolic functions in multiple target organs and its ability to act as an autocrine, paracrine, and endocrine factor. In the liver, FGF21 plays an important role in the regulation of fatty acid oxidation both in the fasted state and in mice consuming a high-fat, low-carbohydrate ketogenic diet...
2016: Annual Review of Physiology
Paul A Welling
More than two dozen types of potassium channels, with different biophysical and regulatory properties, are expressed in the kidney, influencing renal function in many important ways. Recently, a confluence of discoveries in areas from human genetics to physiology, cell biology, and biophysics has cast light on the special function of five different potassium channels in the distal nephron, encoded by the genes KCNJ1, KCNJ10, KCNJ16, KCNMA1, and KCNN3. Research aimed at understanding how these channels work in health and go awry in disease has transformed our understanding of potassium balance and provided new insights into mechanisms of renal sodium handling and the maintenance of blood pressure...
2016: Annual Review of Physiology
Robert P Dickson, John R Erb-Downward, Fernando J Martinez, Gary B Huffnagle
Although the notion that "the normal lung is free from bacteria" remains common in textbooks, it is virtually always stated without citation or argument. The lungs are constantly exposed to diverse communities of microbes from the oropharynx and other sources, and over the past decade, novel culture-independent techniques of microbial identification have revealed that the lungs, previously considered sterile in health, harbor diverse communities of microbes. In this review, we describe the topography and population dynamics of the respiratory tract, both in health and as altered by acute and chronic lung disease...
2016: Annual Review of Physiology
Mamta Rai, Fabio Demontis
Homeostatic systems mount adaptive responses to meet the energy demands of the cell and to compensate for dysfunction in cellular compartments. Such surveillance systems are also active at the organismal level: Nutrient and stress sensing in one tissue can lead to changes in other tissues. Here, we review the emerging understanding of the role of skeletal muscle in regulating physiological homeostasis and disease progression in other tissues. Muscle-specific genetic interventions can induce systemic effects indirectly, via changes in the mass and metabolic demand of muscle, and directly, via the release of muscle-derived cytokines (myokines) and metabolites (myometabolites) in response to nutrients and stress...
2016: Annual Review of Physiology
Henrik Mouritsen, Dominik Heyers, Onur Güntürkün
Migratory birds can navigate over tens of thousands of kilometers with an accuracy unobtainable for human navigators. To do so, they use their brains. In this review, we address how birds sense navigation- and orientation-relevant cues and where in their brains each individual cue is processed. When little is currently known, we make educated predictions as to which brain regions could be involved. We ask where and how multisensory navigational information is integrated and suggest that the hippocampus could interact with structures that represent maps and compass information to compute and constantly control navigational goals and directions...
2016: Annual Review of Physiology
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