New Findings Concerning Vertebrate Porin

Abstract

Eukaryotic porin can be considered to be a good candidate for forming the channel component of the protein complex which, depending on the approach used, may realize its expression either as the outwardly-rectifying depolarization-induced chloride channel or as the volume-sensitive organic osmolyte-anion channel. As a basis for this proposition, we point to a series of correspondences in properties between mammalian porin and the ORDIC channel complex. Specifically, mammalian porin is expressed in the plasmalemma of different cells and chloride channels can be blocked by anti-human porin antibodies in astrocytes and endothelial cells. There is an indication of colocalisation of human porin and the cystic fibrosis (CF) gene product, CFTR, in the apical region of epithelial cells. The primary structure of porin from a CF patient was found to be normal. Cytosol and amniotic fluid fractions influence the channel characteristics of mammalian porin. Channel-active mammalian porin binds ATP and the stilbene disulphonate grouping of the chloride channel inhibitor DIDS. Human porin in black membranes is a pathway for taurine, and biogenic polyamines reduce the voltage dependence of human porin. Assuming the relationship between human porin and the ORDIC channel/VSOAC complex, studies on plasmalemma-integrated human porin have a relevance for CF research. In addition, we refer to a case study on a child with encephalomyopathy in which porin could not be detected using monoclonal anti-human porin antibodies. Our studies were based on purified and sequenced human porin from different cells and from different cell compartments. In addition, we raised antibodies against mature human porin or synthetic parts of the molecule. This provided a firm foundation for our topochemical work with which we were able to establish the multi-topological expression of eukaryotic porin channels. The data are summarized and discussed.

Opening of plasma membrane voltage-dependent anion channels (VDAC) precedes caspase activation in neuronal apoptosis induced by toxic stimuli

“…25 However, several reports, using different techniques, have shown VDAC-like channels in the plasma membrane of multiple cell types, including neurons. [14][15][16][26][27][28] A major argument against the presence of functional VDACs in the plasma membrane has been that this would result in increased membrane permeability that would not be compatible with cell survival. Therefore, as suggested by Yu and Forte, 25 it is likely that these channels are not functional under normal conditions.…”

The Voltage-dependent Anion Channel (VDAC) Binds Tissue-type Plasminogen Activator and Promotes Activation of Plasminogen on the Cell Surface

“…t-PA binds via its fibronectin type I finger domain, which is located between amino acids Ile 5 and Asn 37 , to a domain in VDAC including amino acids 20 GYGFG 24 . Binding of t-PA to VDAC is facilitated by exposure of its NH 2 -terminal region, which in the plasma membrane is facing toward the surface of the cell (63). Pg binding to VDAC induces closure of the channel, whereas t-PA may be involved in the opening of the channel.…”

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

“…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.…”