Cytoplasmic retention sites in p190RhoGEF confer anti-apoptotic activity to an EGFP-tagged protein

Junhua Wu, Jinbin Zhai, Hong Lin, Zhenying Nie, Wei Wen Ge, Laura García-Bermejo, Ruth J. Muschel, William W. Schlaepfer, Rafaela Cañete-Soler

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

p190RhoGEF is a large multi-functional protein with guanine nucleotide exchange (GEF) activity. The C-terminal region of p190RhoGEF is a highly interactive domain that binds multiple factors, including proteins with anti-apoptotic activities. We now report that transfection of EGFP-tagged p190RhoGEF protects Neuro 2a cells from stress-induced apoptosis and that anti-apoptotic activity is localized to cytoplasmic retention sequences (CRS-1 and CRS-2) in the C-terminal region of p190RhoGEF. Cytoplasmic retention is conferred to an EGFP fluorescent marker when fused to either CRS-1 or CRS-2. Both cytoplasmic retention and anti-apoptotic activity are lost by deleting CRS-1 and CRS-2 in the p190RhoGEF sequence and can be recovered by restoring either CRS-1 or CRS-2 to the EGFP-tagged sequence. Since the CRS-1 and CRS-2 contain the JIP-1 and 14-3-3 binding sites, we propose that anti-apoptotic activity may be conferred by the binding of p190RhoGEF to JIP-1 or 14-3-3, possibly by altering their interactive properties or nucleocytoplasmic movements. Taken together, our findings support a model whereby multiple interactions of p190RhoGEF confer homeostatic properties to differentiated neurons and may link neuronal homeostasis to the regulation of NF-L expression.

Original languageEnglish (US)
Pages (from-to)27-38
Number of pages12
JournalMolecular Brain Research
Volume117
Issue number1
DOIs
StatePublished - Sep 10 2003
Externally publishedYes

Keywords

  • Anti-apoptosis
  • Cytoplasmic retention
  • Neuronal homeostasis
  • Nucleocytoplasmic movements
  • p190RhoGEF

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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