Skip to main content

The voltage-dependent anion channel (VDAC) binds tissue-type plasminogen activator and promotes activation of plasminogen on the cell surface.

Publication ,  Journal Article
Gonzalez-Gronow, M; Ray, R; Wang, F; Pizzo, SV
Published in: J Biol Chem
January 4, 2013

The voltage-dependent anion channel (VDAC), a major pore-forming protein in the outer membrane of mitochondria, is also found in the plasma membrane of a large number of cells where in addition to its role in regulating cellular ATP release and volume control it is important for maintaining redox homeostasis. Cell surface VDAC is a receptor for plasminogen kringle 5, which promotes partial closure of the channel. In this study, we demonstrate that VDAC binds tissue-type plasminogen activator (t-PA) on human neuroblastoma SK-N-SH cells. Binding of t-PA to VDAC induced a decrease in K(m) and an increase in the V(max) for activation of its substrate, plasminogen (Pg). This resulted in accelerated Pg activation when VDAC, t-PA, and Pg were bound together. VDAC is also a substrate for plasmin; hence, it mimics fibrin activity. Binding of t-PA to VDAC occurs between a t-PA fibronectin type I finger domain located between amino acids Ile(5) and Asn(37) and a VDAC region including amino acids (20)GYGFG(24). These VDAC residues correspond to a GXXXG repeat motif commonly found in amyloid β peptides that is necessary for aggregation when these peptides form fibrillar deposits on the cell surface. Furthermore, we also show that Pg kringle 5 is a substrate for the NADH-dependent reductase activity of VDAC. This ternary complex is an efficient proteolytic complex that may facilitate removal of amyloid β peptide deposits from the normal brain and cell debris from injured brain tissue.

Duke Scholars

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

January 4, 2013

Volume

288

Issue

1

Start / End Page

498 / 509

Location

United States

Related Subject Headings

  • Voltage-Dependent Anion Channels
  • Tissue Plasminogen Activator
  • Protein Binding
  • Plasminogen
  • Models, Genetic
  • Kinetics
  • Humans
  • Hot Temperature
  • Fibrinolysis
  • Fibrinolysin
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gonzalez-Gronow, M., Ray, R., Wang, F., & Pizzo, S. V. (2013). The voltage-dependent anion channel (VDAC) binds tissue-type plasminogen activator and promotes activation of plasminogen on the cell surface. J Biol Chem, 288(1), 498–509. https://doi.org/10.1074/jbc.M112.412502
Gonzalez-Gronow, Mario, Rupa Ray, Fang Wang, and Salvatore V. Pizzo. “The voltage-dependent anion channel (VDAC) binds tissue-type plasminogen activator and promotes activation of plasminogen on the cell surface.J Biol Chem 288, no. 1 (January 4, 2013): 498–509. https://doi.org/10.1074/jbc.M112.412502.
Gonzalez-Gronow, Mario, et al. “The voltage-dependent anion channel (VDAC) binds tissue-type plasminogen activator and promotes activation of plasminogen on the cell surface.J Biol Chem, vol. 288, no. 1, Jan. 2013, pp. 498–509. Pubmed, doi:10.1074/jbc.M112.412502.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

January 4, 2013

Volume

288

Issue

1

Start / End Page

498 / 509

Location

United States

Related Subject Headings

  • Voltage-Dependent Anion Channels
  • Tissue Plasminogen Activator
  • Protein Binding
  • Plasminogen
  • Models, Genetic
  • Kinetics
  • Humans
  • Hot Temperature
  • Fibrinolysis
  • Fibrinolysin