Glycerophosphodiesterase GDE2/GDPD5 affects pancreas differentiation in zebrafish
| Autor: | Michiel van Veen, Laurie A. Mans, Elisa Matas-Rico, Jason van Pelt, Wouter H. Moolenaar, Anastassis Perrakis, Anna-Pavlina G. Haramis |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
GDE2 Embryo Nonmammalian Organogenesis Recombinant Fusion Proteins Green Fluorescent Proteins Glycerophosphodiesterase Notch signaling pathway Regulator Motility Cell fate determination Biochemistry Morpholinos 03 medical and health sciences Protein Domains medicine Animals Humans Insulin Pancreas development RNA Messenger Pancreas Zebrafish Phylogeny Sequence Homology Amino Acid biology Phosphoric Diester Hydrolases Gene Expression Regulation Developmental Cell Biology Zebrafish Proteins biology.organism_classification Embryonic stem cell GDPD5 Peptide Fragments Transmembrane protein Cell biology Isoenzymes HEK293 Cells 030104 developmental biology medicine.anatomical_structure Gene Knockdown Techniques |
| Zdroj: | International Journal of Biochemistry and Cell Biology, 94, 71. Elsevier Limited |
| ISSN: | 1357-2725 |
| Popis: | Notch signaling plays an essential role in the proliferation, differentiation and cell fate determination of various tissues, including the developing pancreas. One regulator of the Notch pathway is GDE2 (or GDPD5), a transmembrane ecto-phosphodiesterase that cleaves GPI-anchored proteins at the plasma membrane, including a Notch ligand regulator. Here we report that Gdpd5-knockdown in zebrafish embryos leads to developmental defects, particularly, impaired motility and reduced pancreas differentiation, as shown by decreased expression of insulin and other pancreatic markers. Exogenous expression of human GDE2, but not catalytically dead GDE2, similarly leads to developmental defects. Human GDE2 restores insulin expression in Gdpd5a-depleted zebrafish embryos. Importantly, zebrafish Gdpd5 orthologues localize to the plasma membrane where they show catalytic activity against GPI-anchored GPC6. Thus, our data reveal functional conservation between zebrafish Gdpd5 and human GDE2, and suggest that strict regulation of GDE2 expression and catalytic activity is critical for correct embryonic patterning. In particular, our data uncover a role for GDE2 in regulating pancreas differentiation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect