Inactivation of expressed and conducting rCx46 hemichannels by phosphorylation

Ngezahayo, Anaclet; Zeilinger, Carsten; Todt, Ingo; Marten, Irene; Kolb, Hans‐Albert

doi:10.1007/s004240050681

Cited by 25 publications

(15 citation statements)

References 7 publications

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“…We focus exclusively on Cx43 in this discussion as it is the most widely studied. For limited information on other connexin isoforms, we refer the reader to [24,26,71,72,76,100,103,115,134,161,193,204,205,212,226]. …”

Section: Determinants Of Junctional and Channel Permeability: Gatimentioning

confidence: 99%

Structural basis for the selective permeability of channels made of communicating junction proteins

Ek‐Vitorín¹,

Burt²

2013

Biochimica et Biophysica Acta (BBA) - Biomembranes

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The open state(s) of gap junction channels is evident from their permeation by small ions in response to an applied intercellular (transjunctional/transchannel) voltage gradient. That an open channel allows variable amounts of current to transit from cell-to-cell in the face of a constant intercellular voltage difference indicates channel open/closing can be complete or partial. The physiological significance of such open state options is, arguably, the main concern of junctional regulation. Because gap junctions are permeable to many substances, it is sensible to inquire whether and how each open state influences the intercellular diffusion of molecules as valuable as, but less readily detected than current-carrying ions. Presumably, structural changes perceived as shifts in channel conductivity would significantly alter the transjunctional diffusion of molecules whose limiting diameter approximates the pore’s limiting diameter. Moreover, changes in junctional permeability to some molecules might occur without evident changes in conductivity, either at macroscopic or single channel level. Open gap junction channels allow the exchange of cytoplasmic permeants between contacting cells by simple diffusion. The identity of such permeants, and the functional circumstances and consequences of their junctional exchange presently constitute the most urgent (and demanding) themes of the field. Here, we consider the necessity for regulating this exchange, the possible mechanism(s) and structural elements likely involved in such regulation, and how regulatory phenomena could be perceived as changes in chemical vs. electrical coupling; an overall reflection on our collective knowledge of junctional communication is then applied to suggest new avenues of research.

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Section: Determinants Of Junctional and Channel Permeability: Gatimentioning

confidence: 99%

Structural basis for the selective permeability of channels made of communicating junction proteins

Ek‐Vitorín¹,

Burt²

2013

Biochimica et Biophysica Acta (BBA) - Biomembranes

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“…The altered immunoblot pattern is associated with an increase in phosphorylation at Ser118, suggesting that phosphorylation leads to channel closure (12). Rat Cx46 hemichannels are also modulated by PKC phosphorylation; OAG reduces the amplitude of hemichannel currents and leads to their inactivation after prolonged incubation, an effect that can be inhibited by PKC inhibitors (106). PKC␥ and Cx46 have been reported to co-localize in the equatorial and cortical regions of rat lenses, and 10% of the total PKC␥ in lens cortex was co-precipitated with antiCx46 antisera (139).…”

Section: Lens Gap Junctions and Oxidative Stress 345mentioning

confidence: 99%

Oxidative Stress, Lens Gap Junctions, and Cataracts

Berthoud

Beyer

2009

Antioxidants & Redox Signaling

217

141

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The eye lens is constantly subjected to oxidative stress from radiation and other sources. The lens has several mechanisms to protect its components from oxidative stress and to maintain its redox state, including enzymatic pathways and high concentrations of ascorbate and reduced glutathione. With aging, accumulation of oxidized lens components and decreased efficiency of repair mechanisms can contribute to the development of lens opacities or cataracts. Maintenance of transparency and homeostasis of the avascular lens depend on an extensive network of gap junctions. Communication through gap junction channels allows intercellular passage of molecules (up to 1 kDa) including antioxidants. Lens gap junctions and their constituent proteins, connexins (Cx43, Cx46, and Cx50), are also subject to the effects of oxidative stress. These observations suggest that oxidative stress-induced damage to connexins (and consequent altered intercellular communication) may contribute to cataract formation. Antioxid. Redox Signal. 11, 339-353. 339The Eye Lens

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“…In Xenopus oocytes exogenously expressing Cx46, protein kinase C (PKC) directly phosphorylates Cx46, resulting in reduced Cx46 hemichannel-mediated currents [50,51]. Similarly, reconstituted Cx43 hemichannels in liposomes exhibited reduced permeability in response to PKC-mediated phosphorylation of serine 368 [52].…”

Section: Triggers For Hemichannel Openingmentioning

confidence: 99%

Paracrine signaling through plasma membrane hemichannels

Wang

Bock

Decrock

et al. 2013

Biochimica et Biophysica Acta (BBA) - Biomembranes

187

191

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Plasma membrane hemichannels composed of connexin (Cx) proteins are essential components of gap junction channels but accumulating evidence suggests functions of hemichannels beyond the communication provided by junctional channels. Hemichannels not incorporated into gap junctions, called unapposed hemichannels, can open in response to a variety of signals, electrical and chemical, thereby forming a conduit between the cell’s interior and the extracellular milieu. Open hemichannels allow the bidirectional passage of ions and small metabolic or signaling molecules of below 1–2 kDa molecular weight. In addition to connexins, hemichannels can also be formed by pannexin (Panx) proteins and current evidence suggests that Cx26, Cx32, Cx36, Cx43 and Panx1, form hemichannels that allow the diffusive release of paracrine messengers. In particular, the case is strong for ATP but substantial evidence is also available for other messengers like glutamate and prostaglandins or metabolic substances like NAD+ or glutathione. While this field is clearly in expansion, evidence is still lacking at essential points of the paracrine signaling cascade that includes not only messenger release, but also downstream receptor signaling and consequent functional effects. The data available at this moment largely derives from in vitro experiments and still suffers from the difficulty of separating the functions of connexin-based hemichannels from gap junctions and from pannexin hemichannels. However, messengers like ATP or glutamate have universal roles in the body and further defining the contribution of hemichannels as a possible release pathway is expected to open novel avenues for better understanding their contribution to a variety of physiological and pathological processes. This article is part of a Special Issue entitled: The Communicating junctions, roles and dysfunctions.

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Inactivation of expressed and conducting rCx46 hemichannels by phosphorylation

Cited by 25 publications

References 7 publications

Structural basis for the selective permeability of channels made of communicating junction proteins

Structural basis for the selective permeability of channels made of communicating junction proteins

Oxidative Stress, Lens Gap Junctions, and Cataracts

Paracrine signaling through plasma membrane hemichannels

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