Evidence for secretory pathway localization of a voltage-dependent anion channel isoform.
Voltage-dependent anion channels (VDACs) are pore-forming proteins (porins) that form the major pathway for movement of adenine nucleotides through the outer mitochondrial membrane. Electrophysiological studies indicate that VDAC-like channel activity is also prevalent in the cell membranes of many mammalian cells. However, the multitopological localization of porins outside the mitochondrion has remained an extremely controversial issue. Herein, we show that usage of two alternative first exons of the murine VDAC-1 gene leads to expression of two porins differing within their N termini. One porin (plasmalemmal VDAC-1) harboring a hydrophobic leader peptide is primarily targeted through the Golgi apparatus to the cell membrane. In contrast, the second isoform lacking the N-terminal leader (mitochondrial VDAC-1) is translocated more efficiently into the outer mitochondrial membrane. Thus, our data provide unique genetic evidence in favor of a multitopological localization of a mitochondrial porin.
Buettner
R
R
Institute of Pathology, University Hospital Rheinisch-Westfälische Technische Hochschule Aachen, Pauwelstrasse 30, D-52074 Aachen, Germany.
Papoutsoglou
G
G
Scemes
E
E
Spray
D C
DC
Dermietzel
R
R
D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D018076:DNA, Complementary; D007150:Immunohistochemistry; D051379:Mice; D008969:Molecular Sequence Data; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D018272:Porins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism; D050995:Voltage-Dependent Anion Channel 1; D050994:Voltage-Dependent Anion Channels
D018076:DNA, Complementary; D018272:Porins; D020033:Protein Isoforms; D012333:RNA, Messenger; C494763:Vdac1 protein, mouse; C494764:Vdac1 protein, rat; D050994:Voltage-Dependent Anion Channels; D050995:Voltage-Dependent Anion Channel 1