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Wiley Interdisciplinary Reviews : Membrane Transport and Signaling

Subscription journal
ISSN (Online) 2190-4618
Published by John Wiley and Sons

[1587 journals]

Aquaporin‐4 orthogonal arrays of particles from a physiological and pathophysiological point of view
- Abstract: Aquaporin‐4 (AQP4) is the neuromuscular water channel that is also expressed at the basolateral membranes of other cell types in kidney, stomach, and lung. In skeletal muscle, AQP4 is found at the sarcolemma of fast‐twitch fibers and its function is strictly correlated with the glycolytic metabolism. In the central nervous system, AQP4 is expressed at the basolateral membranes of ependymal cells, and is highly concentrated at the glial end‐foot processes surrounding blood vessels and forming the glia limitans, as well as at the nonend‐foot glial processes of the granule cell layer in the cerebellum. AQP4 plasma membrane organization is different from other aquaporins (AQPs). AQP4 is expressed as two major polypeptides called M1 and M23. These two isoforms form heterotetramers appearing in the plasma membrane as intramembrane particles (IMPs) observable by freeze‐fracture electron microscopy. Such tetrameric organization is common to all other AQPs. In the case of AQP4, however, multiple IMPs further aggregate to form structures called orthogonal arrays of particles (OAPs). The relative abundance of M23 and M1 in vivo is the major determinant for the formation of OAPs of different sizes. The function of AQP4 aggregation into OAPs under normal conditions is still not completely understood. Interestingly, there are several reports indicating that OAPs are involved in different neuromuscular diseases. In particular, the OAP‐related diseases that have attracted more attention are Duchenne muscular distrophy and, more recently, neuromyelitis optica, the two pathological conditions in which OAPs are involved in completely different ways. WIREs Membr Transp Signal 2013. doi: 10.1002/wmts.86 For further resources related to this article, please visit the WIREs website.
Connexins, gap junctions, and glia
- Abstract: Neurons and glial cells are the two main classes of cells present in brain. There are four classes of glial cells in the brain that differ by their origin, morphology, and function: microglia, oligodendrocytes, NG2 (nerve/glia antigen 2) cells, and astrocytes. Microglial cells, which are derived from the mesoderm, represent approximately 10% of glia and are the resident immune cells of the central nervous system (CNS). Three subclasses compose the macroglia and are derived from the ectoderm. As an overview one can consider that: (1) the oligodendrocytes are mainly involved in the myelination of axons, (2) the NG2 cells comprise oligodendrocyte precursor cells but they are also multipotential cells, although this issue is still debated, and (3) finally, astrocytes are the predominant glial cells in the brain that establish active interactions with neurons and the vascular system. With the exception of NG2 cells, all glial cells are characterized by the expression of gap junction proteins (connexins) with specific features and properties. In addition, a number of neuropathological disorders involve changes in Cx expression and channel function. WIREs Membr Transp Signal 2013. doi: 10.1002/wmts.87 For further resources related to this article, please visit the WIREs website.
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At the center of the circle: purinergic signaling in the autocrine loops of pancreatic islets
- Abstract: The endocrine pancreas is essential for monitoring and regulating the metabolic status of the body by sensing changes in glucose and free fatty acids and respond by secreting hormones such as insulin and glucagon. Although pancreatic islets only make up a small percentage of the pancreas mass, its malfunction causes severe disease. Despite insulin treatment, and the development of novel antidiabetic drugs, diabetes is still one of the most costly and invaliding diseases, leaving an open arena for drug target discovery within the endocrine pancreas. Purinergic receptors are a class of receptors, which has already been utilized as a successful antithrombotic drug target used in secondary prevention after myocardial infarction. The versatility and broad expression of these receptors make them interesting for pharmacological manipulation in treatment of disease. Purinergic receptors include four G‐protein coupled adenosine receptors (A1, A2A, A2B, and A3), eight G‐protein coupled nucleotide (ATP, ADP, UTP, UDP, UDP‐glucose) gated receptors (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14), and finally seven ATP‐gated ion channels (P2X1‐7). Ectonucleotidases degrade nucleotides to their di‐ and mono derivatives, which in turn can stimulate their favored P2 receptor. Adenosine monophosphate (AMP) is finally hydrolyzed to adenosine, which in turn can act on adenosine receptors. Each P2Y receptor couples to different G‐proteins leading to different intracellular pathways downstream of stimulation. WIREs Membr Transp Signal 2013. doi: 10.1002/wmts.82 For further resources related to this article, please visit the WIREs website. The authors have declared no conflicts of interest for this article.
Cannabinoid receptors and pain
- Abstract: Activation of both cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptors reduces nociceptive processing in acute and chronic animal models of pain. In addition, nociceptive processing is tonically modulated by endogenous cannabinoids (endocannabinoids, ECs). This review examines the role of cannabinoids and ECs in the brain stem–spinal pathway of pain inhibition. Preclinical studies evaluating cannabinoids in neuropathic pain management are also reviewed. Pharmacological tools modulating the interaction of cannabinoids with its receptors and the treatment of pain by the augmentation of EC levels, specifically anandamide, are discussed. Particular attention is attributed to neuropathic pain in which pharmacological manipulation resulting in EC accumulation can be protective and produce antinociception, thereby making the system an attractive therapeutic target. Finally, the therapeutic value of cannabinoids in clinical research is summarized. WIREs Membr Transp Signal 2013. doi: 10.1002/wmts.83 For further resources related to this article, please visit the WIREs website. The authors have declared no conflicts of interest for this article.
The birth of the journal: the first anniversary of WIREs MTS
- Abstract: WIREs Membr Transp Signal 2013. doi: 10.1002/wmts.81 For further resources related to this article, please visit the WIREs website.