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Functional Characterization of Na+/H+ Exchangers of Intracellular Compartments Using Proton-killing Selection to Express Them at the Plasma Membrane
07:38

Functional Characterization of Na+/H+ Exchangers of Intracellular Compartments Using Proton-killing Selection to Express Them at the Plasma Membrane

Published on: March 30, 2015

Novel membrane traffic steps regulate the exocytosis of the Menkes disease ATPase

Christian Cobbold1, Sreenivasan Ponnambalam, Michael J Francis

  • 1Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7BN, UK.

Human Molecular Genetics
|October 24, 2002
PubMed

Insights

Menkes disease protein (MNK) moves from the Golgi to the cell surface when copper is present. This transport relies on protein kinase A and Cdc42 GTPase, revealing a new pathway for MNK export.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Menkes disease protein (ATP7A or MNK) is a P-type ATPase crucial for copper ion transport.
  • MNK regulates copper translocation across intracellular membranes within the secretory pathway.

Purpose of the Study:

  • To investigate the intracellular localization and trafficking of endogenous MNK.
  • To elucidate the regulatory mechanisms governing MNK transport to the plasma membrane in response to copper.

Main Methods:

  • Utilized cultured cell lines to observe endogenous MNK localization and response to copper.
  • Employed dominant-negative mutant protein kinase D and protein kinase A inhibitors.
  • Expressed constitutively active Rho GTPases (Cdc42, Rac1, RhoA) and WASp.

Main Results:

  • Endogenous MNK localizes to the distal Golgi and translocates to the plasma membrane upon copper exposure.
  • MNK transport is independent of protein kinase D but sensitive to protein kinase A inhibition.
  • Cdc42 GTPase and WASp are essential for copper-stimulated MNK trafficking to the cell surface.

Conclusions:

  • Copper-induced MNK translocation to the plasma membrane involves a novel TGN-to-plasma membrane trafficking pathway.
  • This pathway is regulated by protein kinase A and the Cdc42 GTPase signaling cascade.
  • Findings provide new insights into the cellular export mechanism of MNK.

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