title: PLD1 regulates Xenopus convergent extension movements by mediating Frizzled7 endocytosis for Wnt/PCP signal activation.
abstract: Phospholipase D (PLD) is involved in the regulation of receptor-associated signaling, cell movement, cell adhesion and endocytosis. However, its physiological role in vertebrate development remains poorly understood. In this study, we show that PLD1 is required for the convergent extension (CE) movements during Xenopus gastrulation by activating Wnt/PCP signaling. Xenopus PLD1 protein is specifically enriched in the dorsal region of Xenopus gastrula embryo and loss or gain-of-function of PLD1 induce defects in gastrulation and CE movements. These defective phenotypes are due to impaired regulation of Wnt/PCP signaling pathway. Biochemical and imaging analysis using Xenopus tissues reveal that PLD1 is required for Fz7 receptor endocytosis upon Wnt11 stimulation. Moreover, we show that Fz7 endocytosis depends on dynamin and regulation of GAP activity of dynamin by PLD1 via its PX domain is crucial for this process. Taken together, our results suggest that PLD1 acts as a new positive mediator of Wnt/PCP signaling by promoting Wnt11-induced Fz7 endocytosis for precise regulation of Xenopus CE movements.
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, San31, Hyoja Dong, Pohang, Kyungbuk 790-784, Republic of Korea.
authors.forename: Hyeyoon
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, San31, Hyoja Dong, Pohang, Kyungbuk 790-784, Republic of Korea.
authors.forename: Seung Joon
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Division of Life Science and Pioneer Research Center for Protein Network Exploration, Korea Basic Science Institute, 52 Eoeun-dong, Yuseong-gu, Daejeon 305-333, Republic of Korea; Department of Functional Genomics, University of Science and Technology (UST), Daejeon 305-333, Republic of Korea.
authors.forename: Gun-Hwa
authors.initials: GH
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, San31, Hyoja Dong, Pohang, Kyungbuk 790-784, Republic of Korea.
authors.forename: Inchul
authors.initials: I
authors.lastname: Yeo
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, San31, Hyoja Dong, Pohang, Kyungbuk 790-784, Republic of Korea. Electronic address: jkh@postech.ac.kr.
authors.forename: Jin-Kwan
authors.initials: JK
authors.lastname: Han
mesh_terms: D000818:Animals; D034281:Dynamins / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D005775:Gastrula / Q000378:metabolism; D054262:Gastrulation / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006801:Humans; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology*
chemical_list: C492040:Fzd7 protein, Xenopus; D043562:Receptors, G-Protein-Coupled; D051153:Wnt Proteins; D029867:Xenopus Proteins; C512785:wnt11b protein, Xenopus; D010739:Phospholipase D; C106801:phospholipase D1; D034281:Dynamins
keywords: Convergent extension movements; Endocytosis; Frizzled7; Gastrulation; Phospholipase D; Wnt/PCP signaling; Xenopus laevis