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Intracellular cysteine 346 is essentially involved in regulating Panx1 channel activity.

ABSTRACT: Pannexins constitute a family of proteins exhibiting predominantly hemichannel activity. Pannexin channels have been suggested to participate in a wide spectrum of biological functions such as propagation of calcium waves, release of IL-1?, and responses to ischemic conditions. At present, the molecular mechanisms regulating pannexin hemichannel activity are essentially unknown. Because cysteines have been shown to constitute key elements in regulating hemichannel properties of the connexin-type we performed site-directed mutagenesis of intracellular cysteine residues of Panx1. Cysteine to serine exchange (Cys ? Ser) at the C-terminal position amino acid 346 led to a constitutively leaky hemichannel and subsequently to cell death. Increased channel activity was demonstrated by dye uptake and electrophysiological profiling in injected Xenopus laevis oocytes and transfected N2A cells. Mutations of the remaining intracellular cysteines did not result in major changes of Panx1 channel properties. From these data we conclude that the Cys-346 residue is important for proper functioning of the Panx1 channel.

SUBMITTER: Bunse S

PROVIDER: S-EPMC2992277 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Intracellular cysteine 346 is essentially involved in regulating Panx1 channel activity.

Bunse Stefanie S Schmidt Matthias M Prochnow Nora N Zoidl Georg G Dermietzel Rolf R

The Journal of biological chemistry 20100909 49

Pannexins constitute a family of proteins exhibiting predominantly hemichannel activity. Pannexin channels have been suggested to participate in a wide spectrum of biological functions such as propagation of calcium waves, release of IL-1β, and responses to ischemic conditions. At present, the molecular mechanisms regulating pannexin hemichannel activity are essentially unknown. Because cysteines have been shown to constitute key elements in regulating hemichannel properties of the connexin-type ...[more]

PMID: 20829356

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Project description:Low?density lipoprotein receptor?related protein 6 (LRP6) promotes metastasis in numerous types of cancer; however, its role in trophoblast cells has been less frequently reported. In the present study, the effects of up? and downregulation of LRP6 on trophoblast cells were investigated accordingly. The study aimed to develop a therapeutic target for gestational choriocarcinoma. The expression levels of LRP6 in pre?eclampsia (PE) tissues, trophoblast cell lines and gestational choriocarcinoma cells were determined using reverse transcription?quantitative polymerase chain reaction (RT?qPCR) assay. Double?luciferase reporter analysis was conducted to detect the regulatory gene of LRP6. Furthermore, the proliferative, migratory and invasive abilities of trophoblasts and gestational choriocarcinoma cells were determined by CCK?8, wound healing, and Transwell assays, respectively. The expression levels of the genes and proteins of interest [matrix metalloproteinase (MMP)?2, MMP?9, tissue inhibitor of metalloproteinase?1 (TIMP?1), and TIMP?2] associated with tumor cell invasion were measured by performing RT?qPCR and western blotting, respectively. The National Center for Biotechnology Information database revealed that LRP6 was relatively highly expressed in placental tissues, but was poorly expressed in PE tissues and trophoblast cell lines. The upregulation of LRP6 not only increased the activity, migration and invasion of trophoblast cells, but it also promoted the expression of MMP?2 and MMP?9, whereas it inhibited the expression levels of TIMP?1 and TIMP?2. Such results followed the opposite trend to those of downregulation of LRP6 in gestational choriocarcinoma cells. Moreover, LRP6 was predicted to be the target gene for microRNA (miR)?346, which was highly expressed in PE tissues and trophoblast cell lines. The present study also revealed that LRP6 could reverse the effects of miR?346 on the proliferation, migration and invasion of trophoblast cells. Therefore, considered collectively, the results of the present study have demonstrated that LRP6 is involved in the proliferation, migration and invasion of trophoblast cells via miR?346, and that LRP6 may serve as a potential target in cancer treatment.

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Intracellular cysteine 346 is essentially involved in regulating Panx1 channel activity.

Publications

Intracellular cysteine 346 is essentially involved in regulating Panx1 channel activity.

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