The novel plasminogen receptor, plasminogen receptor(KT) (Plg-R(KT)), regulates catecholamine release

J Biol Chem. 2011 Sep 23;286(38):33125-33. doi: 10.1074/jbc.M111.218693. Epub 2011 Jul 27.

Abstract

Neurotransmitter release by catecholaminergic cells is negatively regulated by prohormone cleavage products formed from plasmin-mediated proteolysis. Here, we investigated the expression and subcellular localization of Plg-R(KT), a novel plasminogen receptor, and its role in catecholaminergic cell plasminogen activation and regulation of catecholamine release. Prominent staining with anti-Plg-R(KT) mAb was observed in adrenal medullary chromaffin cells in murine and human tissue. In Western blotting, Plg-R(KT) was highly expressed in bovine adrenomedullary chromaffin cells, human pheochromocytoma tissue, PC12 pheochromocytoma cells, and murine hippocampus. Expression of Plg-R(KT) fused in-frame to GFP resulted in targeting of the GFP signal to the cell membrane. Phase partitioning, co-immunoprecipitation with urokinase-type plasminogen activator receptor (uPAR), and FACS analysis with antibody directed against the C terminus of Plg-R(KT) were consistent with Plg-R(KT) being an integral plasma membrane protein on the surface of catecholaminergic cells. Cells stably overexpressing Plg-R(KT) exhibited substantial enhancement of plasminogen activation, and antibody blockade of non-transfected PC12 cells suppressed plasminogen activation. In functional secretion assays, nicotine-evoked [(3)H]norepinephrine release from cells overexpressing Plg-R(KT) was markedly decreased (by 51 ± 2%, p < 0.001) when compared with control transfected cells, and antibody blockade increased [(3)H]norepinephrine release from non-transfected PC12 cells. In summary, Plg-R(KT) is present on the surface of catecholaminergic cells and functions to stimulate plasminogen activation and modulate catecholamine release. Plg-R(KT) thus represents a new mechanism and novel control point for regulating the interface between plasminogen activation and neurosecretory cell function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adrenal Medulla / cytology
  • Adrenal Medulla / drug effects
  • Adrenal Medulla / metabolism
  • Animals
  • Antibodies / pharmacology
  • Catecholamines / metabolism*
  • Cattle
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Enzyme Activation / drug effects
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Mice
  • PC12 Cells
  • Plasminogen / metabolism*
  • Protein Transport / drug effects
  • Rats
  • Receptors, Cell Surface / antagonists & inhibitors
  • Receptors, Cell Surface / metabolism*

Substances

  • Antibodies
  • Catecholamines
  • PLG-R(KT) protein, mouse
  • Receptors, Cell Surface
  • Green Fluorescent Proteins
  • Plasminogen