FAM209 associates with DPY19L2, and is required for sperm acrosome biogenesis and fertility in mice

Infertility afflicts up to 15% of couples globally each year with men a contributing factor in 50% of these cases. Globozoospermia is a rare condition found in infertile men, which is characterized by defective acrosome biogenesis leading to the production of round-headed sperm. Here, we report that...

Descripción completa

Detalles Bibliográficos
Autores principales: Castaneda, Julio M., Shimada, Keisuke, Satouh, Yuhkoh, Yu, Zhifeng, Devlin, Darius J., Ikawa, Masahito, Matzuk, Martin M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627553/
https://www.ncbi.nlm.nih.gov/pubmed/34471926
http://dx.doi.org/10.1242/jcs.259206
_version_ 1784606859194269696
author Castaneda, Julio M.
Shimada, Keisuke
Satouh, Yuhkoh
Yu, Zhifeng
Devlin, Darius J.
Ikawa, Masahito
Matzuk, Martin M.
author_facet Castaneda, Julio M.
Shimada, Keisuke
Satouh, Yuhkoh
Yu, Zhifeng
Devlin, Darius J.
Ikawa, Masahito
Matzuk, Martin M.
author_sort Castaneda, Julio M.
collection PubMed
description Infertility afflicts up to 15% of couples globally each year with men a contributing factor in 50% of these cases. Globozoospermia is a rare condition found in infertile men, which is characterized by defective acrosome biogenesis leading to the production of round-headed sperm. Here, we report that family with sequence similarity 209 (Fam209) is required for acrosome biogenesis in mouse sperm. FAM209 is a small transmembrane protein conserved among mammals. Loss of Fam209 results in fertility defects that are secondary to abnormalities in acrosome biogenesis during spermiogenesis, reminiscent of globozoospermia. Analysis of the FAM209 proteome identified DPY19L2, whose human orthologue is involved in the majority of globozoospermia cases. Although mutations in human and mouse Dpy19l2 have been shown to cause globozoospermia, no in vivo interacting partners of DPY19L2 have been identified until now. FAM209 colocalizes with DPY19L2 at the inner nuclear membrane to maintain the developing acrosome. Here, we identified FAM209 as the first interacting partner of DPY19L2, and the second protein that is essential for acrosome biogenesis that localizes to the inner nuclear membrane.
format Online
Article
Text
id pubmed-8627553
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher The Company of Biologists Ltd
record_format MEDLINE/PubMed
spelling pubmed-86275532021-11-30 FAM209 associates with DPY19L2, and is required for sperm acrosome biogenesis and fertility in mice Castaneda, Julio M. Shimada, Keisuke Satouh, Yuhkoh Yu, Zhifeng Devlin, Darius J. Ikawa, Masahito Matzuk, Martin M. J Cell Sci Research Article Infertility afflicts up to 15% of couples globally each year with men a contributing factor in 50% of these cases. Globozoospermia is a rare condition found in infertile men, which is characterized by defective acrosome biogenesis leading to the production of round-headed sperm. Here, we report that family with sequence similarity 209 (Fam209) is required for acrosome biogenesis in mouse sperm. FAM209 is a small transmembrane protein conserved among mammals. Loss of Fam209 results in fertility defects that are secondary to abnormalities in acrosome biogenesis during spermiogenesis, reminiscent of globozoospermia. Analysis of the FAM209 proteome identified DPY19L2, whose human orthologue is involved in the majority of globozoospermia cases. Although mutations in human and mouse Dpy19l2 have been shown to cause globozoospermia, no in vivo interacting partners of DPY19L2 have been identified until now. FAM209 colocalizes with DPY19L2 at the inner nuclear membrane to maintain the developing acrosome. Here, we identified FAM209 as the first interacting partner of DPY19L2, and the second protein that is essential for acrosome biogenesis that localizes to the inner nuclear membrane. The Company of Biologists Ltd 2021-11-01 /pmc/articles/PMC8627553/ /pubmed/34471926 http://dx.doi.org/10.1242/jcs.259206 Text en © 2021. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Castaneda, Julio M.
Shimada, Keisuke
Satouh, Yuhkoh
Yu, Zhifeng
Devlin, Darius J.
Ikawa, Masahito
Matzuk, Martin M.
FAM209 associates with DPY19L2, and is required for sperm acrosome biogenesis and fertility in mice
title FAM209 associates with DPY19L2, and is required for sperm acrosome biogenesis and fertility in mice
title_full FAM209 associates with DPY19L2, and is required for sperm acrosome biogenesis and fertility in mice
title_fullStr FAM209 associates with DPY19L2, and is required for sperm acrosome biogenesis and fertility in mice
title_full_unstemmed FAM209 associates with DPY19L2, and is required for sperm acrosome biogenesis and fertility in mice
title_short FAM209 associates with DPY19L2, and is required for sperm acrosome biogenesis and fertility in mice
title_sort fam209 associates with dpy19l2, and is required for sperm acrosome biogenesis and fertility in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627553/
https://www.ncbi.nlm.nih.gov/pubmed/34471926
http://dx.doi.org/10.1242/jcs.259206
work_keys_str_mv AT castanedajuliom fam209associateswithdpy19l2andisrequiredforspermacrosomebiogenesisandfertilityinmice
AT shimadakeisuke fam209associateswithdpy19l2andisrequiredforspermacrosomebiogenesisandfertilityinmice
AT satouhyuhkoh fam209associateswithdpy19l2andisrequiredforspermacrosomebiogenesisandfertilityinmice
AT yuzhifeng fam209associateswithdpy19l2andisrequiredforspermacrosomebiogenesisandfertilityinmice
AT devlindariusj fam209associateswithdpy19l2andisrequiredforspermacrosomebiogenesisandfertilityinmice
AT ikawamasahito fam209associateswithdpy19l2andisrequiredforspermacrosomebiogenesisandfertilityinmice
AT matzukmartinm fam209associateswithdpy19l2andisrequiredforspermacrosomebiogenesisandfertilityinmice