Functional implications of calcium permeability of the channel formed by pannexin 1.
Although human pannexins (PanX) are homologous to gap junction molecules, their physiological function in vertebrates remains poorly understood. Our results demonstrate that overexpression of PanX1 results in the formation of Ca(2+)-permeable gap junction channels between adjacent cells, thus, allowing direct intercellular Ca(2+) diffusion and facilitating intercellular Ca(2+) wave propagation. More intriguingly, our results strongly suggest that PanX1 may also form Ca(2+)-permeable channels in the endoplasmic reticulum (ER). These channels contribute to the ER Ca(2+) leak and thereby affect the ER Ca(2+) load. Because leakage remains the most enigmatic of those processes involved in intracellular calcium homeostasis, and the molecular nature of the leak channels is as yet unknown, the results of this work provide new insight into calcium signaling mechanisms. These results imply that for vertebrates, a new protein family, referred to as pannexins, may not simply duplicate the connexin function but may also provide additional pathways for intra- and intercellular calcium signaling and homeostasis.
Vanden Abeele
Fabien
F
Institut National de la Santé et de la Recherche Médicale, U800, Equipe labellisée par la Ligue Contre le Cancer, Universite des Sciences et Technologies de Lille, Villeneuve d'Ascq Cedex, F-59655 France.
Bidaux
Gabriel
G
Gordienko
Dmitri
D
Beck
Benjamin
B
Panchin
Yuri V
YV
Baranova
Ancha V
AV
Ivanov
Dmitry V
DV
Skryma
Roman
R
Prevarskaya
Natalia
N
D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000502:physiology*; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D004058:Diffusion; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005456:Fluorescent Dyes; D017629:Gap Junctions / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D015220:Calcium Channels; D017630:Connexins; D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins; C492764:PANX1 protein, human; D012333:RNA, Messenger; D002118:Calcium