Sperm proteins SOF1, TMEM95, and SPACA6 are required for sperm-oocyte fusion in mice

Noda, Taichi; Lu, Yonggang; Fujihara, Yoshitaka et al.

Proceedings of the National Academy of Sciences of the United States of America, 2020, 117(21), 11493-11502

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Identifier to cite or link to this item: https://hdl.handle.net/11094/78546

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Title
Sperm proteins SOF1, TMEM95, and SPACA6 are required for sperm-oocyte fusion in mice
Creator
NRID
1000050712551 1000050712551
CreatorName
Noda, Taichi
NRID
1000000817033 1000000817033
ORCID
0000-0003-0198-8906 0000-0003-0198-8906
researchmap permalink
yonggang-lu yonggang-lu
Scopus Author ID
57210966053 57210966053
CreatorName
Lu, Yonggang
NRID
1000070578848 1000070578848
CreatorName
Fujihara, Yoshitaka
CreatorName
Oura, Seiya
CreatorName
Koyano, Takayuki
CreatorName
Kobayashi, Sumire
CreatorName
Matzuk, Martin M.
NRID
1000020304066 1000020304066
ORCID
0000-0001-9859-6217 0000-0001-9859-6217
researchmap permalink
read0054910 read0054910
Scopus Author ID
16689054500 16689054500
CreatorName
Ikawa, Masahito
Subject
Infertility
IZUMO1
LLCFC1
Sperm-oocyte fusion
Transgenic
Description
Noda, T., Lu, Y., Fujihara, Y., Oura, S., Koyano, T., Kobayashi, S., . . . Ikawa, M. (2020). Sperm proteins SOF1, TMEM95, and SPACA6 are required for sperm-oocyte fusion in mice. Proceedings of the National Academy of Sciences of the United States of America, 117(21) doi:10.1073/pnas.1922650117
Abstract
Sperm-oocyte membrane fusion is one of the most important events for fertilization. So far, IZUMO1 and Fertilization Influencing Membrane Protein (FIMP) on the sperm membrane and CD9 and JUNO (IZUMO1R/FOLR4) on the oocyte membrane have been identified as fusion-required proteins. However, the molecular mechanisms for sperm-oocyte fusion are still unclear. Here, we show that testis-enriched genes, sperm-oocyte fusion required 1 (Sof1/Llcfc1/1700034O15Rik), transmembrane protein 95 (Tmem95), and sperm acrosome associated 6 (Spaca6), encode sperm proteins required for sperm-oocyte fusion in mice. These knockout (KO) spermatozoa carry IZUMO1 but cannot fuse with the oocyte plasma membrane, leading to male sterility. Transgenic mice which expressed mouse Sof1, Tmem95, and Spaca6 rescued the sterility of Sof1, Tmem95, and Spaca6 KO males, respectively. SOF1 and SPACA6 remain in acrosome-reacted spermatozoa, and SPACA6 translocates to the equatorial segment of these spermatozoa. The coexpression of SOF1, TMEM95, and SPACA6 in IZUMO1-expressing cultured cells did not enhance their ability to adhere to the oocyte membrane or allow them to fuse with oocytes. SOF1, TMEM95, and SPACA6 may function cooperatively with IZUMO1 and/or unknown fusogens in sperm-oocyte fusion.
Publisher
National Academy of Sciences
Source Title
Proceedings of the National Academy of Sciences of the United States of America
Volume (Issue)
117(21)
Page
11493-11502
Date of Issued
2020-05-26
Language
English
Handle URL
https://hdl.handle.net/11094/78546
PISSN
00278424
eISSN
10916490
NCID
AA11726874
Relation.isIdenticalTo
DOI (Publisher Version)
https://doi.org/10.1073/pnas.1922650117
PMID
32393636
Access Rights
open access
CopyRight
© 2020 the Author(s). Published by PNAS. This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version
Version of Record
Category
学術雑誌論文 Journal Article