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Single-Molecule Imaging of Nuclear Transport
12:13

Single-Molecule Imaging of Nuclear Transport

Published on: June 9, 2010

Dissecting the signaling events that impact classical nuclear import and target nuclear transport factors

Mohamed Kodiha1, Dan Tran, Andreea Morogan

  • 1Department of Physiology, McGill University, Montreal, Canada.

Plos One
|December 31, 2009
PubMed
Abstract

Insights

Oxidative stress impacts nuclear import by altering the localization and modification of key transport proteins, mediated by MEK-ERK and PI3K-Akt signaling pathways.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Signaling pathways like MEK-ERK and PI3K-Akt are crucial for cell survival during oxidant exposure.
  • Oxidative stress influences physiological and pathophysiological processes involving nuclear transport.
  • The precise impact of oxidative stress on nuclear trafficking remains incompletely understood.

Purpose of the Study:

  • To investigate how oxidative stress affects nucleocytoplasmic trafficking.
  • To elucidate the molecular mechanisms by which stress signaling pathways regulate nuclear transport factors.
  • To define the role of MEK and PI3K signaling in controlling the localization and modification of nuclear transport components.

Main Methods:

  • Cells were exposed to the oxidant diethyl maleate to induce oxidative stress.
  • Activation of MEK-ERK and PI3K-Akt cascades was monitored.
  • Subcellular localization of importin-alpha, CAS, Nup153, and Nup88 was quantified using advanced imaging techniques.
  • Post-translational modifications of transport factors were analyzed.

Main Results:

  • Oxidative stress and MEK/PI3K signaling inhibited classical nuclear import.
  • Specific localization profiles of nuclear transport factors were identified in the nucleus, cytoplasm, and nuclear envelope.
  • Stress-induced changes in transport factor distribution and post-translational modifications (phosphorylation, O-GlcNAc) were observed.
  • Phosphorylation of importin-alpha, CAS, Nup153, and Nup88, and O-GlcNAc modification of Nup153 increased under oxidative stress.

Conclusions:

  • Classical nuclear import is complexly regulated by oxidative stress, MEK, and PI3K signaling.
  • Key nuclear transport factors are specifically targeted by these signaling pathways during stress.
  • This study provides insights into how cells adapt their nuclear transport machinery in response to oxidative challenges.

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