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Cellular and Molecular Life Sciences

, Volume 72, Issue 15, pp 2823–2851 | Cite as

Connexin and pannexin signaling pathways, an architectural blueprint for CNS physiology and pathology?

  • Elke Decrock
  • Marijke De Bock
  • Nan Wang
  • Geert Bultynck
  • Christian Giaume
  • Christian C. Naus
  • Colin R. Green
  • Luc Leybaert
Multi-author review

Abstract

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.

Keywords

Central nervous system Connexin Pannexin Glia Neuron Blood–brain barrier Physiology Pathology 

Abbreviations

ATP

Adenosine triphosphate

AQP4

Aquaporin-4

BBB

Blood–brain barrier

[Ca2+]e

Extracellular calcium concentration

[Ca2+]i

Cytoplasmic calcium concentration

Cbx

Carbenoxolone

CNS

Central nervous system

CP

Cortical plate

CT

C-terminal tail

Cx

Connexin

GABA

Gamma-aminobutyric acid

GJC

Gap junction channel

GJIC

Gap junctional intercellular communication

HC

Hemichannel

ICW

Intercellular calcium wave

IL-1β

Interleukin-1β

IP3

Inositol 1,4,5-trisphosphate

IZ

Intermediate zone

[K+]e

Extracellular potassium concentration

KO

Knockout

(m)GluR

(Metabotropic) glutamate receptor

LTD

Long-term depression

LTP

Long-term potentiation

MW

Molecular weight

NGVU

Neuro-glio-vascular unit

NMDAR

N-Methyl-d-aspartate receptor

NPC

Neural progenitor cell

Panx

Pannexin

RMS

Rostral migratory stream

SGZ

Subgranular zone

SP

Subplate

SVZ

Subventricular zone

TNF-α

Tumor necrosis factor-α

VZ

Ventricular zone

Notes

Acknowledgments

This work is supported by the Fund for Scientific Research Flanders (FWO-Vlaanderen), Belgium (Grants G.0298.11, G.0571.12, G.0A54.13 and G.0320.15) and the Interuniversity Attraction Poles Program (Belgian Science Policy, project P7/10 and P7/13) granted to L.L. C.C.N holds a Canada Research Chair. The work was also supported by the New Zealand Marsden Fund, The CatWalk Trust, the New Zealand Neurological Foundation, and the Health Research Council of New Zealand (C.R.G).

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest. C.R.G is a founding scientist of CoDa Therapeutics, Inc. which has intellectual property related to connexin channel modulation for therapeutic purposes.

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Copyright information

© Springer Basel 2015

Authors and Affiliations

  • Elke Decrock
    • 1
  • Marijke De Bock
    • 1
  • Nan Wang
    • 1
  • Geert Bultynck
    • 2
  • Christian Giaume
    • 3
    • 4
    • 5
  • Christian C. Naus
    • 6
  • Colin R. Green
    • 7
  • Luc Leybaert
    • 1
  1. 1.Physiology Group, Department of Basic Medical SciencesGhent UniversityGhentBelgium
  2. 2.Laboratory of Molecular and Cellular Signalling, Department of Cellular and Molecular MedicineKU LeuvenLouvainBelgium
  3. 3.Collège de France, Center for Interdisciplinary Research in Biology (CIRB)/Centre National de la Recherche ScientifiqueUnité Mixte de Recherche 7241/Institut National de la Santé et de la Recherche Médicale U1050Paris Cedex 05France
  4. 4.University Pierre et Marie CurieParisFrance
  5. 5.MEMOLIFE Laboratory of Excellence and Paris Science Lettre Research UniversityParisFrance
  6. 6.Department of Cellular and Physiological Sciences, Faculty of MedicineUniversity of British ColumbiaVancouverCanada
  7. 7.Department of OphthalmologyThe University of AucklandAucklandNew Zealand

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