Dynamin 2-dependent endocytosis is essential for mouse oocyte development and fertility.


Journal

FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484

Informations de publication

Date de publication:
04 2020
Historique:
received: 29 08 2019
revised: 18 01 2020
accepted: 29 01 2020
pubmed: 18 2 2020
medline: 20 1 2021
entrez: 18 2 2020
Statut: ppublish

Résumé

During folliculogenesis, oocytes are dependent on metabolic and molecular support from surrounding somatic cells. Here, we examined the role of the dynamin (DNM) family of mechanoenzymes in mediating endocytotic uptake into growing follicular oocytes. We found DNM1 and DNM2 to be highly expressed in growing follicular oocytes as well as in mature germinal vesicle (GV) and metaphase II (MII) stage oocytes. Moreover, oocyte-specific conditional knockout (cKO) of DNM2 (DNM2Δ) led to complete sterility, with follicles arresting at the preantral stage of development. In addition, DNM2Δ ovaries were characterized by disrupted follicular growth as well as oocyte and follicle apoptosis. Further, the loss of DNM activity, either through DNM2 cKO or through pharmacological inhibition (Dyngo 6a) led to the impairment of endocytotic pathways in preantral oocytes as well as in mature GV and MII oocytes, respectively. Loss of DNM activity resulted in the redistribution of endosomes and the misslocalization of clathrin and actin, suggesting dysfunctional endocytosis. Notably, there was no observable effect on the fertility of DNM1Δ females. Our study has provided new insight into the complex and dynamic nature of oocyte growth during folliculogenesis, suggesting a role for DNM2 in mediating the endocytotic events that are essential for oocyte development.

Identifiants

pubmed: 32065700
doi: 10.1096/fj.201902184R
doi:

Substances chimiques

Dynamin I EC 3.5.1.50
DNM2 protein, mouse EC 3.6.5.5
Dynamin II EC 3.6.5.5

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

5162-5177

Informations de copyright

© 2020 University of Newcastle. The FASEB Journal published by Wiley Periodicals, Inc. © 2020 Federation of American Societies for Experimental Biology.

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Auteurs

Bettina P Mihalas (BP)

School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW, Australia.
Priority Research Centre for Reproductive Science, University of Newcastle, Callaghan, NSW, Australia.
Pregnancy and Reproduction Program, Hunter Medial Research Institute, New Lambton Heights, NSW, Australia.

Kate A Redgrove (KA)

School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW, Australia.
Priority Research Centre for Reproductive Science, University of Newcastle, Callaghan, NSW, Australia.
Pregnancy and Reproduction Program, Hunter Medial Research Institute, New Lambton Heights, NSW, Australia.

Ilana R Bernstein (IR)

School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW, Australia.
Priority Research Centre for Reproductive Science, University of Newcastle, Callaghan, NSW, Australia.
Pregnancy and Reproduction Program, Hunter Medial Research Institute, New Lambton Heights, NSW, Australia.

Mark J Robertson (MJ)

School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW, Australia.
Priority Research Centre in Chemical Biology, University of Newcastle, Callaghan, NSW, Australia.

Adam McCluskey (A)

School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW, Australia.
Priority Research Centre in Chemical Biology, University of Newcastle, Callaghan, NSW, Australia.

Brett Nixon (B)

School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW, Australia.
Priority Research Centre for Reproductive Science, University of Newcastle, Callaghan, NSW, Australia.
Pregnancy and Reproduction Program, Hunter Medial Research Institute, New Lambton Heights, NSW, Australia.

Janet E Holt (JE)

Priority Research Centre for Reproductive Science, University of Newcastle, Callaghan, NSW, Australia.
School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, NSW, Australia.

Eileen A McLaughlin (EA)

School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW, Australia.
Priority Research Centre for Reproductive Science, University of Newcastle, Callaghan, NSW, Australia.
Pregnancy and Reproduction Program, Hunter Medial Research Institute, New Lambton Heights, NSW, Australia.
School of Science, Western Sydney University, Penrith, NSW, Australia.
School of Biological Sciences, The University of Auckland, Auckland, New Zealand.

Jessie M Sutherland (JM)

Priority Research Centre for Reproductive Science, University of Newcastle, Callaghan, NSW, Australia.
Pregnancy and Reproduction Program, Hunter Medial Research Institute, New Lambton Heights, NSW, Australia.
School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, NSW, Australia.

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