Lentil Lectin Enriched Microsomes from the Plasma Membrane of the Human B-Lymphocyte Cell Line H2LCL Carry a Heavy Load of Type-1 Porin

Eben-Brunnen, Jana; Reymann, Susanne; Awni, Lewa Adil; Cole, T.; Hellmann, Thea; Hellmann, Klaus P.; Paetzold, Gabriele; Kleineke, Jochen; Thinnes, Friedrich P.; Götz, H.; Hilschmann, Norbert

doi:10.1515/bchm.1998.379.12.1419

Cited by 15 publications

(11 citation statements)

References 26 publications

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“…A large number of research groups have indeed detected the presence of VDAC protein in the plasma membrane of various cells (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26), and several genetic mechanisms for targeting the same protein to such different locations as mitochondrial outer membrane and plasmalemma have been postulated (14,27).…”

Section: Discussionmentioning

confidence: 99%

“…This hypothesis was based on the similarity of shared biophysical properties, such as the large unitary conductance and bell-shaped voltage dependence of the maxianion channel and mitochondrial VDAC (13)(14)(15)(16)(17)(18). Corroborating this idea, numerous groups have reported the presence of VDAC protein in the plasma membrane of various cell types (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). A possible mechanism for targeting of the same protein to different locations has been suggested by Buettner et al (14).…”

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confidence: 99%

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Genetic Demonstration That the Plasma Membrane Maxianion Channel and Voltage-dependent Anion Channels Are Unrelated Proteins

Sabirov

Sheiko

Liu

et al. 2006

Journal of Biological Chemistry

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The maxianion channel is widely expressed in many cell types, where it fulfills a general physiological function as an ATP-conductive gate for cell-to-cell purinergic signaling. Establishing the molecular identity of this channel is crucial to understanding the mechanisms of regulated ATP release. A mitochondrial porin (voltage-dependent anion channel (VDAC)) located in the plasma membrane has long been considered as the molecule underlying the maxianion channel activity, based upon similarities in the biophysical properties of these two channels and the purported presence of VDAC protein in the plasma membrane. We have deleted each of the three genes encoding the VDAC isoforms individually and collectively and demonstrate that maxianion channel (ϳ400 picosiemens) activity in VDAC-deficient mouse fibroblasts is unaltered. The channel activity is similar in VDAC1/VDAC3-double-deficient cells and in double-deficient cells with the VDAC2 protein depleted by RNA interference. VDAC deletion slightly down-regulated, but never abolished, the swelling-induced ATP release. The lack of correlation between VDAC protein expression and maxianion channel activity strongly argues against the long held hypothesis of plasmalemmal VDAC being the maxianion channel.Purinergic signaling is a widespread phenomenon of general biological significance, and mechanisms accounting for ATP release from cells remain a contentious issue (1). We have recently identified a maxianion channel as a nanoscopic pore (2) well suited to function as the ATPreleasing pathway (3, 4). This pore accounts for the swelling-induced ATP release from mouse mammary C127 cells (5, 6) and NaCl-dependent ATP-mediated signaling from macula densa to mesangial cells during tubuloglomerular feedback in the kidney (7). In addition, the same pore is operational in swelling-, ischemia-, and hypoxia-induced ATP release from neonatal rat cardiomyocytes (8).The maxianion channel has been observed in a wide variety of cell types and exhibits roughly uniform behavior (9), suggesting that it has a general physiological function. Although the molecular identity of the maxianion channel is not yet firmly established, it is widely held that a voltage-dependent anion channel (VDAC) 2 located in the plasmalemma that normally functions in the mitochondrial outer membrane (10 -12) is the most likely candidate protein. This hypothesis was based on the similarity of shared biophysical properties, such as the large unitary conductance and bell-shaped voltage dependence of the maxianion channel and mitochondrial VDAC (13-18). Corroborating this idea, numerous groups have reported the presence of VDAC protein in the plasma membrane of various cell types (13-26). A possible mechanism for targeting of the same protein to different locations has been suggested by Buettner et al. (14). They reported the existence of an alternative first exon in the murine vdac-1 gene that encodes a different leader peptide at the N terminus, a signal that purportedly targets the protein to the plasma membran...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Genetic Demonstration That the Plasma Membrane Maxianion Channel and Voltage-dependent Anion Channels Are Unrelated Proteins

Sabirov

Sheiko

Liu

et al. 2006

Journal of Biological Chemistry

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“…At the same time, we demonstrated for the first time the multi-topological expression of the channel, meanwhile supported by different approaches [1,2,3]. The first indication on the function of plasmlemma-integrated porin came from studies on the Cl -flux of cells from the renal loop of Henle, which described a putative Cl -channel molecule with a molecular mass of 31 kDa [21], i.e.…”

Section: Discussionmentioning

confidence: 78%

“…Eukaryotic porin or the voltage-dependent anion-selective channel (VDAC), is expressed in different cell compartments [1,2,3]. The elucidation of the function of porin channels in the plasma membrane is not yet complete.…”

Section: Introductionmentioning

confidence: 99%

Gadolinium as an opener of the outwardly rectifying Cl - channel (ORCC). Is there relevance for cystic fibrosis therapy?

Thinnes

Walter

Hellmann

et al. 2001

Pfl�gers Archiv European Journal of Physiology

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There is indirect evidence that the plasmalemma-integrated eukaryotic porin (the voltage-dependent anion-selective channel, VDAC) functions as the outwardly rectifying chloride channel (ORCC). The channel, which is believed to play a role in cell volume regulation, appears to be relevant for cystic fibrosis (CF) therapy, in that it may function as an alternative Cl(-) channel. In the present study we showed first that Gd(3+) altered the voltage dependence of human type-1 porin incorporated into artificial planar lipid bilayers. Next, using a light-scattering approach on transformed normal or CF human B-lymphocytes in hypotonic Ringer solution, we found slightly differing regulatory volume decrease (RVD) curves for the cell lines under study. Addition of 15-60 microM GdCl3 in hypotonic Ringer increased light scattering, pointing to cell swelling beyond normal values. RVD was not observed in those experiments. A corresponding effect was seen in isotonic Ringer containing GdCl3. In either osmotic situation Gd(3+)-induced cell swelling was abolished by monoclonal mouse anti-human type-1 porin antibodies. Agonist and antibody effects were dose dependent. Finally, videocamera-monitored control experiments with adherent HeLa cells verified the direct effect of the agonist on cell swelling in hypo- or isotonic situations and its prevention by the antibodies. We conclude that GdCl3 opens plasmalemma-integrated porin channels, allowing ions to following their gradients, resulting in cell swelling. Since respiratory epithelium expresses porin channels in the apical membrane, the use of gadolinium to activate ORCC may represent a new therapeutic approach in CF.

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“…The statements of the paper pay credit to early controversial experimental data on mammalian or fungal VDAC structure [4,5], respectively. In addition, data concerning cell membrane-embedded type-1 VDAC also point to the accessibility of the N-terminal stretch channel from outside, in this case from the cell surface [1,6]. In this situation VDAC channels should be in a fully closed state, most likely achieved by interaction(s) with channel modulators [for further details see: http://www.futhin.de].…”

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On a fully closed state of native human type-1 VDAC enriched in Nonidet P40

Thinnes¹,

Burckhardt²

2012

Molecular Genetics and Metabolism

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Lentil Lectin Enriched Microsomes from the Plasma Membrane of the Human B-Lymphocyte Cell Line H2LCL Carry a Heavy Load of Type-1 Porin

Cited by 15 publications

References 26 publications

Genetic Demonstration That the Plasma Membrane Maxianion Channel and Voltage-dependent Anion Channels Are Unrelated Proteins

Genetic Demonstration That the Plasma Membrane Maxianion Channel and Voltage-dependent Anion Channels Are Unrelated Proteins

Gadolinium as an opener of the outwardly rectifying Cl - channel (ORCC). Is there relevance for cystic fibrosis therapy?

On a fully closed state of native human type-1 VDAC enriched in Nonidet P40

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