title: Pannexin channels in ATP release and beyond: an unexpected rendezvous at the endoplasmic reticulum.
abstract: The pannexin (Panx) family of proteins, which is co-expressed with connexins (Cxs) in vertebrates, was found to be a new GJ-forming protein family related to invertebrate innexins. During the past ten years, different studies showed that Panxs mainly form hemichannels in the plasma membrane and mediate paracrine signalling by providing a flux pathway for ions such as Ca²(+), for ATP and perhaps for other compounds, in response to physiological and pathological stimuli. Although the physiological role of Panxs as a hemichannel was questioned, there is increasing evidence that Panx play a role in vasodilatation, initiation of inflammatory responses, ischemic death of neurons, epilepsy and in tumor suppression. Moreover, it is intriguing that Panxs may also function at the endoplasmic reticulum (ER) as intracellular Ca²(+)-leak channel and may be involved in ER-related functions. Although the physiological significance and meaning of such Panx-regulated intracellular Ca²(+) leak requires further exploration, this functional property places Panx at the centre of many physiological and pathophysiological processes, given the fundamental role of intracellular Ca²(+) homeostasis and dynamics in a plethora of physiological processes. In this review, we therefore want to focus on Panx as channels at the plasma membrane and at the ER membranes with a particular emphasis on the potential implications of the latter in intracellular Ca²(+) signalling.
authors.affiliation: Laboratory of Molecular and Cellular Signalling, K.U. Leuven, Campus Gasthuisberg O/N-1 bus 802, B-3000 Leuven, Belgium.
authors.forename: Catheleyne
authors.initials: C
authors.lastname: D'hondt
authors.forename: Raf
authors.initials: R
authors.lastname: Ponsaerts
authors.forename: Humbert
authors.initials: H
authors.lastname: De Smedt
authors.forename: Mathieu
authors.initials: M
authors.lastname: Vinken
authors.forename: Elke
authors.initials: E
authors.lastname: De Vuyst
authors.forename: Marijke
authors.initials: M
authors.lastname: De Bock
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Vera
authors.initials: V
authors.lastname: Rogiers
authors.forename: Luc
authors.initials: L
authors.lastname: Leybaert
authors.forename: Bernard
authors.initials: B
authors.lastname: Himpens
authors.forename: Geert
authors.initials: G
authors.lastname: Bultynck
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D017630:Connexins / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D051379:Mice
chemical_list: D017630:Connexins; D000255:Adenosine Triphosphate