XGAP, an ArfGAP, Is Required for Polarized Localization of PAR Proteins and Cell Polarity in Xenopus Gastrulation

• DOI: 10.1016/j.devcel.2006.04.019
• Publication Date: 2006-07-11T14:02:05Z
• Authors: Junko Hyodo-Miura; Takamasa S. Yamamoto; Akiko C. Hyodo; Shun-Ichiro Iemura; Morioh Kusakabe; Eisuke Nishida; Tohru Natsume; Naoto Ueno
• Keywords: Xenopus; Molecular Sequence Data; DEVBIO; Models, Biological; Oligodeoxyribonucleotides, Antisense; 03 medical and health sciences; Cell Movement; Animals; Humans; Phosphorylation; Protein Kinase C; 0303 health sciences; Base Sequence; GTPase-Activating Proteins; Cell Polarity; Gastrula; Recombinant Proteins; Protein Structure, Tertiary; 14-3-3 Proteins; CELLBIO; Carrier Proteins; Developmental Biology; HeLa Cells; Protein Binding; Signal Transduction

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.