caa a22 4500 606177604 CHVBK 20210128100752.0 cr unu---uuuuu 210128e20150801xx s 000 0 eng 10.1007/s00018-015-1962-7 doi (NATIONALLICENCE)springer-10.1007/s00018-015-1962-7 Connexin and pannexin signaling pathways, an architectural blueprint for CNS physiology and pathology? [Elektronische Daten] [Elke Decrock, Marijke De Bock, Nan Wang, Geert Bultynck, Christian Giaume, Christian Naus, Colin Green, Luc Leybaert] The central nervous system (CNS) is composed of a highly heterogeneous population of cells. Dynamic interactions between different compartments (neuronal, glial, and vascular systems) drive CNS function and allow to integrate and process information as well as to respond accordingly. Communication within this functional unit, coined the neuro-glio-vascular unit (NGVU), typically relies on two main mechanisms: direct cell-cell coupling via gap junction channels (GJCs) and paracrine communication via the extracellular compartment, two routes to which channels composed of transmembrane connexin (Cx) or pannexin (Panx) proteins can contribute. Multiple isoforms of both protein families are present in the CNS and each CNS cell type is characterized by a unique Cx/Panx portfolio. Over the last two decades, research has uncovered a multilevel platform via which Cxs and Panxs can influence different cellular functions within a tissue: (1) Cx GJCs enable a direct cell-cell communication of small molecules, (2) Cx hemichannels and Panx channels can contribute to autocrine/paracrine signaling pathways, and (3) different structural domains of these proteins allow for channel-independent functions, such as cell-cell adhesion, interactions with the cytoskeleton, and the activation of intracellular signaling pathways. In this paper, we discuss current knowledge on their multifaceted contribution to brain development and to specific processes in the NGVU, including synaptic transmission and plasticity, glial signaling, vasomotor control, and blood-brain barrier integrity in the mature CNS. By highlighting both physiological and pathological conditions, it becomes evident that Cxs and Panxs can play a dual role in the CNS and that an accurate fine-tuning of each signaling mechanism is crucial for normal CNS physiology. Springer Basel, 2015 Central nervous system nationallicence Connexin nationallicence Pannexin nationallicence Glia nationallicence Neuron nationallicence Blood-brain barrier nationallicence Physiology nationallicence Pathology nationallicence ATP : Adenosine triphosphate nationallicence AQP4 : Aquaporin-4 nationallicence BBB : Blood-brain barrier nationallicence [Ca2+]e : Extracellular calcium concentration nationallicence [Ca2+]i : Cytoplasmic calcium concentration nationallicence Cbx : Carbenoxolone nationallicence CNS : Central nervous system nationallicence CP : Cortical plate nationallicence CT : C-terminal tail nationallicence Cx : Connexin nationallicence GABA : Gamma-aminobutyric acid nationallicence GJC : Gap junction channel nationallicence GJIC : Gap junctional intercellular communication nationallicence HC : Hemichannel nationallicence ICW : Intercellular calcium wave nationallicence IL-1β : Interleukin-1β nationallicence IP3 : Inositol 1,4,5-trisphosphate nationallicence IZ : Intermediate zone nationallicence [K+]e : Extracellular potassium concentration nationallicence KO : Knockout nationallicence (m)GluR : (Metabotropic) glutamate receptor nationallicence LTD : Long-term depression nationallicence LTP : Long-term potentiation nationallicence MW : Molecular weight nationallicence NGVU : Neuro-glio-vascular unit nationallicence NMDAR : N-Methyl-d-aspartate receptor nationallicence NPC : Neural progenitor cell nationallicence Panx : Pannexin nationallicence RMS : Rostral migratory stream nationallicence SGZ : Subgranular zone nationallicence SP : Subplate nationallicence SVZ : Subventricular zone nationallicence TNF-α : Tumor necrosis factor-α nationallicence VZ : Ventricular zone nationallicence Decrock Elke Physiology Group, Department of Basic Medical Sciences, Ghent University, De Pintelaan 185 (Block B, 3rd floor), 9000, Ghent, Belgium aut De Bock Marijke Physiology Group, Department of Basic Medical Sciences, Ghent University, De Pintelaan 185 (Block B, 3rd floor), 9000, Ghent, Belgium aut Wang Nan Physiology Group, Department of Basic Medical Sciences, Ghent University, De Pintelaan 185 (Block B, 3rd floor), 9000, Ghent, Belgium aut Bultynck Geert Laboratory of Molecular and Cellular Signalling, Department of Cellular and Molecular Medicine, KU Leuven, Louvain, Belgium aut Giaume Christian Collège de France, Center for Interdisciplinary Research in Biology (CIRB)/Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7241/Institut National de la Santé et de la Recherche Médicale U1050, 75231, Paris Cedex 05, France aut Naus Christian Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, V6T 1Z3, Vancouver, BC, Canada aut Green Colin Department of Ophthalmology, The University of Auckland, Auckland, New Zealand aut Leybaert Luc Physiology Group, Department of Basic Medical Sciences, Ghent University, De Pintelaan 185 (Block B, 3rd floor), 9000, Ghent, Belgium aut Cellular and Molecular Life Sciences Springer Basel 72/15(2015-08-01), 2823-2851 1420-682X 72:15<2823 2015 72 18 https://doi.org/10.1007/s00018-015-1962-7 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-015-1962-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Decrock Elke Physiology Group, Department of Basic Medical Sciences, Ghent University, De Pintelaan 185 (Block B, 3rd floor), 9000, Ghent, Belgium aut NATIONALLICENCE 700 1- De Bock Marijke Physiology Group, Department of Basic Medical Sciences, Ghent University, De Pintelaan 185 (Block B, 3rd floor), 9000, Ghent, Belgium aut NATIONALLICENCE 700 1- Wang Nan Physiology Group, Department of Basic Medical Sciences, Ghent University, De Pintelaan 185 (Block B, 3rd floor), 9000, Ghent, Belgium aut NATIONALLICENCE 700 1- Bultynck Geert Laboratory of Molecular and Cellular Signalling, Department of Cellular and Molecular Medicine, KU Leuven, Louvain, Belgium aut NATIONALLICENCE 700 1- Giaume Christian Collège de France, Center for Interdisciplinary Research in Biology (CIRB)/Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7241/Institut National de la Santé et de la Recherche Médicale U1050, 75231, Paris Cedex 05, France aut NATIONALLICENCE 700 1- Naus Christian Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, V6T 1Z3, Vancouver, BC, Canada aut NATIONALLICENCE 700 1- Green Colin Department of Ophthalmology, The University of Auckland, Auckland, New Zealand aut NATIONALLICENCE 700 1- Leybaert Luc Physiology Group, Department of Basic Medical Sciences, Ghent University, De Pintelaan 185 (Block B, 3rd floor), 9000, Ghent, Belgium aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/15(2015-08-01), 2823-2851 1420-682X 72:15<2823 2015 72 18