Glycerophosphodiesterase GDE2/GDPD5 affects pancreas differentiation in zebrafish

Michiel van Veen; Laurie A Mans; Elisa Matas-Rico; Jason van Pelt; Anastassis Perrakis; Wouter H Moolenaar; Anna-Pavlina G Haramis

doi:10.1016/j.biocel.2017.11.015

Glycerophosphodiesterase GDE2/GDPD5 affects pancreas differentiation in zebrafish

Int J Biochem Cell Biol. 2018 Jan:94:71-78. doi: 10.1016/j.biocel.2017.11.015. Epub 2017 Dec 22.

Authors

Michiel van Veen¹, Laurie A Mans², Elisa Matas-Rico¹, Jason van Pelt², Anastassis Perrakis³, Wouter H Moolenaar¹, Anna-Pavlina G Haramis⁴

Affiliations

¹ Division of Cell Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
² Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, Leiden, The Netherlands.
³ Division of Biochemistry, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
⁴ Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, Leiden, The Netherlands. Electronic address: a.haramis@biology.leidenuniv.nl.

PMID: 29203233
DOI: 10.1016/j.biocel.2017.11.015

Abstract

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.

Keywords: GDE2; GDPD5; Glycerophosphodiesterase; Insulin; Pancreas development; Zebrafish.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Embryo, Nonmammalian / abnormalities
Embryo, Nonmammalian / diagnostic imaging
Embryo, Nonmammalian / metabolism
Gene Expression Regulation, Developmental*
Gene Knockdown Techniques
Green Fluorescent Proteins / chemistry
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
HEK293 Cells
Humans
Isoenzymes / antagonists & inhibitors
Isoenzymes / chemistry
Isoenzymes / genetics
Isoenzymes / metabolism
Morpholinos / metabolism
Organogenesis*
Pancreas / diagnostic imaging
Pancreas / embryology
Pancreas / metabolism*
Peptide Fragments / antagonists & inhibitors
Peptide Fragments / chemistry
Peptide Fragments / genetics
Peptide Fragments / metabolism
Phosphoric Diester Hydrolases / chemistry
Phosphoric Diester Hydrolases / genetics
Phosphoric Diester Hydrolases / metabolism*
Phylogeny
Protein Domains
RNA, Messenger / antagonists & inhibitors
RNA, Messenger / metabolism
Recombinant Fusion Proteins / chemistry
Recombinant Fusion Proteins / metabolism
Sequence Homology, Amino Acid
Zebrafish
Zebrafish Proteins / antagonists & inhibitors
Zebrafish Proteins / chemistry
Zebrafish Proteins / genetics
Zebrafish Proteins / metabolism*

Substances

Isoenzymes
Morpholinos
Peptide Fragments
RNA, Messenger
Recombinant Fusion Proteins
Zebrafish Proteins
Green Fluorescent Proteins
Phosphoric Diester Hydrolases
glycerophosphodiester phosphodiesterase