Rit GTPase regulates a p38 MAPK-dependent neuronal survival pathway

Weikang Cai, Jennifer L. Rudolph, Tomoko Sengoku, Douglas A. Andres

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Rit, along with Rin and Drosophila Ric, comprises the Rit subfamily of Ras-related small GTPases. Although the cellular functions of many Ras family GTPases are well established, the physiological significance of Rit remains poorly understood. Loss of Rit sensitizes multiple mammalian cell lines and mouse embryonic fibroblasts (MEFs) derived from Rit-/- mice to oxidative stress-mediated apoptosis. However, whether Rit-mediated pro-survival signaling extends to other cell types, particularly neurons, is presently unknown. Here, to examine these issues we generated a transgenic mouse overexpressing constitutively active Rit (RitQ79L) exclusively in neurons, under control of the Synapsin I promoter. Active Rit-expressing hippocampal neurons display a dramatic increase in oxidative stress resistance. Moreover, pharmacological inhibitor studies demonstrate that p38 MAPK, rather than a MEK/ERK signaling cascade, is required for Rit-mediated protection. Together, the present studies identify a critical role for the Rit-p38 MAPK signaling cascade in promoting hippocampal neuron survival following oxidative stress.

Original languageEnglish
Pages (from-to)125-130
Number of pages6
JournalNeuroscience Letters
Volume531
Issue number2
DOIs
StatePublished - Dec 7 2012

Bibliographical note

Funding Information:
We thank Drs. G.-X. Shi, and C. Moncman for helpful discussions. This work was supported by Public Health Service grant NS045103 from the National Institute of Neurological Disorders and Stroke (D.A.A.) and in part by NIH grant P20GM103486 from the National Institute of General Medical Sciences , its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or the NIGMS.

Keywords

  • Hippocampal neuron
  • Ras GTPase
  • Reactive oxygen species (ROS)
  • Stress
  • Survival

ASJC Scopus subject areas

  • General Neuroscience

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