Proteins without transmembrane domains could be anchored to the cell surface for regulating various biological processes when covalently linked to glycosylphosphatidylinositol (GPI) molecules by the GPI transamidase (GPIT) complex. However, it remains poorly understood whether and how the GPIT complex affects primordial germ cell (PGC) development. In this study, we report the important roles of GPI transamidase in PGC migration and development in zebrafish embryos. Mutation of pigu or pigk, both encoding essential GPIT complex subunits, resulted in defective PGC migration with ectopically located PGCs and reduction of PGC counts. Notably, a detailed analysis of filopodia in PGCs revealed the attenuated polarity of filopodia distribution along the migration direction in mutant embryos. PGC transplantation and PGC-specific rescue experiments demonstrated that both PGC and somatic cell-expressed Pigu are required for PGC migration. Furthermore, expression levels of PGC-specific genes decreased in pigu mutant PGCs with the derepression of somatic cell genes. Hence, we propose that the GPIT complex plays a critical role during PGC migration and development.
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http://dx.doi.org/10.1093/jmcb/mjae058 | DOI Listing |
J Mol Cell Biol
December 2024
Laboratory of Molecular Developmental Biology, State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Proteins without transmembrane domains could be anchored to the cell surface for regulating various biological processes when covalently linked to glycosylphosphatidylinositol (GPI) molecules by the GPI transamidase (GPIT) complex. However, it remains poorly understood whether and how the GPIT complex affects primordial germ cell (PGC) development. In this study, we report the important roles of GPI transamidase in PGC migration and development in zebrafish embryos.
View Article and Find Full Text PDFSubcell Biochem
July 2024
CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences (CAS), Shanghai, China.
Glycosylphosphatidylinositol (GPI) anchoring of proteins is a ubiquitous posttranslational modification in eukaryotic cells. GPI-anchored proteins (GPI-APs) play critical roles in enzymatic, signaling, regulatory, and adhesion processes. Over 20 enzymes are involved in GPI synthesis, attachment to client proteins, and remodeling after attachment.
View Article and Find Full Text PDFNat Commun
September 2023
State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences (CAS), University of CAS, Shanghai, China.
Many eukaryotic receptors and enzymes rely on glycosylphosphatidylinositol (GPI) anchors for membrane localization and function. The transmembrane complex GPI-T recognizes diverse proproteins at a signal peptide region that lacks consensus sequence and replaces it with GPI via a transamidation reaction. How GPI-T maintains broad specificity while preventing unintentional cleavage is unclear.
View Article and Find Full Text PDFBiochemistry
July 2022
Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, Michigan 48202, United States.
Glycosylphosphatidylinositol (GPI) anchoring of proteins is a eukaryotic, post-translational modification catalyzed by GPI transamidase (GPI-T). The GPI-T is composed of five membrane-bound subunits: Gpi8, Gaa1, Gpi16, Gpi17, and Gab1. GPI-T has been recalcitrant to structure and function studies because of its complexity and membrane-solubility.
View Article and Find Full Text PDFNat Commun
May 2022
State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of CAS, Chinese Academy of Sciences (CAS), 320 Yueyang Road, 200030, Shanghai, China.
Eukaryotic cells are coated with an abundance of glycosylphosphatidylinositol anchor proteins (GPI-APs) that play crucial roles in fertilization, neurogenesis, and immunity. The removal of a hydrophobic signal peptide and covalent attachment of GPI at the new carboxyl terminus are catalyzed by an endoplasmic reticulum membrane GPI transamidase complex (GPI-T) conserved among all eukaryotes. Here, we report the cryo-electron microscopy (cryo-EM) structure of the human GPI-T at a global 2.
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