title: XGAP, an ArfGAP, is required for polarized localization of PAR proteins and cell polarity in Xenopus gastrulation.
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.
authors.affiliation: Department of Developmental Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Hyodo-Miura
authors.forename: Takamasa S
authors.initials: TS
authors.lastname: Yamamoto
authors.forename: Akiko C
authors.initials: AC
authors.lastname: Hyodo
authors.forename: Shun-Ichiro
authors.initials: S
authors.lastname: Iemura
authors.forename: Morioh
authors.initials: M
authors.lastname: Kusakabe
authors.forename: Eisuke
authors.initials: E
authors.lastname: Nishida
authors.forename: Tohru
authors.initials: T
authors.lastname: Natsume
authors.forename: Naoto
authors.initials: N
authors.lastname: Ueno
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D016764:Cell Polarity / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005775:Gastrula / Q000166:cytology / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014981:Xenopus / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D011994:Recombinant Proteins; D029867:Xenopus Proteins; C115015:PKC-3 protein; D011493:Protein Kinase C