XGAP, an ArfGAP, is required for polarized localization of PAR proteins and cell polarity in Xenopus gastrulation

Dev Cell. 2006 Jul;11(1):69-79. doi: 10.1016/j.devcel.2006.04.019.

Abstract

To dissect the molecular mechanisms underlying convergent extension (CE), a prominent set of cell movements during Xenopus gastrulation, we performed a functional expression screen and identified a GTPase-activating protein for ADP ribosylation factors (ArfGAP), which we termed XGAP. We demonstrated that XGAP is required to confine or restrict the cellular protrusive activity to the mediolateral ends of cells, where XGAP is normally localized, and therefore for the proper intercalation of cells participating in CE. We also demonstrated that a C-terminal conserved domain of XGAP, but not its GAP activity, is required and sufficient for this intracellular localization and function. We further showed that XGAP physically interacts with the known polarity proteins 14-3-3epsilon, aPKC, and PAR-6 and directs them to the mediolateral ends of dorsal mesoderm cells during gastrulation. We propose that XGAP controls CE through the restriction and maintenance of partitioning-defective (PAR) proteins in the regions that harbor protrusive activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / metabolism
  • Animals
  • Base Sequence
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Movement
  • Cell Polarity / physiology*
  • GTPase-Activating Proteins / antagonists & inhibitors
  • GTPase-Activating Proteins / chemistry
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism*
  • Gastrula / cytology
  • Gastrula / metabolism*
  • HeLa Cells
  • Humans
  • Models, Biological
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides, Antisense / genetics
  • Oligodeoxyribonucleotides, Antisense / pharmacology
  • Phosphorylation
  • Protein Binding
  • Protein Kinase C / metabolism
  • Protein Structure, Tertiary
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • Xenopus / embryology*
  • Xenopus / genetics
  • Xenopus / metabolism*
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism*

Substances

  • 14-3-3 Proteins
  • Carrier Proteins
  • GTPase-Activating Proteins
  • Oligodeoxyribonucleotides, Antisense
  • Recombinant Proteins
  • Xenopus Proteins
  • PKC-3 protein
  • Protein Kinase C

Associated data

  • GENBANK/AB195293
  • GENBANK/AB195294
  • GENBANK/AB195295
  • GENBANK/AB195296