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A GEF activity-independent function for nuclear Net1 in Nodal signal transduction and mesendoderm formation

Shi Wei1, Guozhu Ning1, Linwei Li1

  • 1State Key Laboratory of Membrane Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100101, China.

Journal of Cell Science
|August 6, 2017
PubMed

Insights

Nuclear Net1 protein is essential for early embryonic development, regulating mesendoderm formation and Nodal signaling in zebrafish. This function is independent of its previously known RhoA-specific guanine nucleotide exchange factor (GEF) activity.

Area of Science:

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Background:

  • Net1 is an oncoprotein with RhoA-specific guanine nucleotide exchange factor (GEF) activity, typically found in the cytosol of tumor cells.
  • Wild-type Net1 localizes to the nucleus, but its nuclear function remains largely uncharacterized.

Purpose of the Study:

  • To investigate the function of nuclear Net1 during early embryonic development.
  • To elucidate the mechanism by which Net1 influences mesendoderm formation and Nodal signaling.

Main Methods:

  • Utilized zebrafish as a model organism for studying early development.
  • Performed gain- and loss-of-function experiments in zebrafish embryos and mammalian cells.
  • Conducted detailed analyses of protein interactions, including co-immunoprecipitation and recruitment assays.

Main Results:

  • Zebrafish net1 is expressed in mesendoderm precursors during gastrulation and localizes to the nucleus.
  • Nuclear Net1 is critical for mesendoderm formation and Nodal signal transduction, independent of its GEF activity.
  • Net1 interacts with Smad2 in the nucleus, promoting Smad2 activation by enhancing p300 recruitment to the transcriptional complex.

Conclusions:

  • Nuclear Net1 plays a novel, GEF-independent role in regulating mesendoderm development.
  • Net1 facilitates Smad2 transcriptional activity through interaction with Smad2 and p300.
  • This study reveals a new genetic mechanism governing mesendoderm development via nuclear Net1 function.
Keywords:
Mesendoderm formationNet1Nodal signalingSmad2Zebrafish

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