Cytoplasmic cleavage of DPPA3 is required for intracellular trafficking and cleavage-stage development in mice

Seung-Wook Shin; Edgar John Vogt; Maria Jimenez-Movilla; Boris Baibakov; Jurrien Dean

doi:10.1038/s41467-017-01387-6

Cytoplasmic cleavage of DPPA3 is required for intracellular trafficking and cleavage-stage development in mice

Nat Commun. 2017 Nov 21;8(1):1643. doi: 10.1038/s41467-017-01387-6.

Authors

Seung-Wook Shin¹, Edgar John Vogt¹, Maria Jimenez-Movilla², Boris Baibakov¹, Jurrien Dean³

Affiliations

¹ Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD, 20892, USA.
² Department of Cell Biology and Histology, Medical School, University of Murcia, IMIB, 30100, Murcia, Spain.
³ Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD, 20892, USA. jurrien.dean@nih.gov.

Abstract

Degradation of maternal proteins by the ubiquitin-proteasome system (UPS) accompanies the maternal-to-zygotic transition. DPPA3/Stella/PGC7, encoded by a maternal effect gene, is present in the nucleus and cytoplasm of zygotes and has been associated with protecting the female pronucleus from TET3-mediated demethylation. We now report that cytoplasmic DPPA3 is partially cleaved by the ubiquitin-proteasome system and an N-terminus fragment remains in the cytoplasm where it associates with early and re-cycling endosomes. If DPPA3 is absent or if cleavage is prevented, multiple vesicles coalesce/aggregate and markers of lysosomes are decreased. Fertilized eggs develop poorly into blastocysts, which results in significantly decreased fecundity of Dppa3 ^R60A transgenic mice. This phenocopies aspects of Lamp1/2 knockdowns and Dppa3 ^KO embryos can be partially rescued in vitro by DPPA3^1-60 and to a lesser extent by LAMP1/2. Thus, the N-terminus of DPPA3 has a significant role in cytoplasmic vesicular trafficking in addition to its previously reported nuclear function.

Publication types

Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Motifs
Animals
Blastocyst / metabolism
Cell Nucleus / genetics
Cell Nucleus / metabolism
Chromosomal Proteins, Non-Histone
Cytoplasm / genetics
Cytoplasm / metabolism*
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
Dioxygenases
Embryonic Development
Female
Gene Expression Regulation, Developmental
Lysosomal Membrane Proteins / genetics
Lysosomal Membrane Proteins / metabolism
Male
Mice / embryology*
Mice / genetics
Mice / metabolism
Mice, Knockout
Pregnancy
Proteasome Endopeptidase Complex / genetics
Proteasome Endopeptidase Complex / metabolism
Protein Transport
Proteolysis
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism
Repressor Proteins / chemistry
Repressor Proteins / genetics
Repressor Proteins / metabolism*
Zygote / cytology
Zygote / metabolism

Substances

Chromosomal Proteins, Non-Histone
DNA-Binding Proteins
Dppa3 protein, mouse
Lamp1 protein, mouse
Lysosomal Membrane Proteins
Proto-Oncogene Proteins
Repressor Proteins
Dioxygenases
Tet3 protein, mouse
Proteasome Endopeptidase Complex