A Role of TMEM16E Carrying a Scrambling Domain in Sperm Motility
Transmembrane protein 16E (TMEM16E) belongs to the TMEM16 family of proteins that have 10 transmembrane regions and appears to localize intracellularly. Although TMEM16E mutations cause bone fragility and muscular dystrophy in humans, its biochemical function is unknown. In the TMEM16 family, TMEM16...
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| Veröffentlicht in: | Molecular and cellular biology 2016-02, Vol.36 (4), p.645-659 |
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| creator | Gyobu, Sayuri Miyata, Haruhiko Ikawa, Masahito Yamazaki, Daiju Takeshima, Hiroshi Suzuki, Jun Nagata, Shigekazu |
| description | Transmembrane protein 16E (TMEM16E) belongs to the TMEM16 family of proteins that have 10 transmembrane regions and appears to localize intracellularly. Although TMEM16E mutations cause bone fragility and muscular dystrophy in humans, its biochemical function is unknown. In the TMEM16 family, TMEM16A and -16B serve as Ca
2+
-dependent Cl
−
channels, while TMEM16C, -16D, -16F, -16G, and -16J support Ca
2+
-dependent phospholipid scrambling. Here, we show that TMEM16E carries a segment composed of 35 amino acids homologous to the scrambling domain in TMEM16F. When the corresponding segment of TMEM16A was replaced by this 35-amino-acid segment of TMEM16E, the chimeric molecule localized to the plasma membrane and supported Ca
2+
-dependent scrambling. We next established TMEM16E-deficient mice, which appeared to have normal skeletal muscle. However, fertility was decreased in the males. We found that TMEM16E was expressed in germ cells in early spermatogenesis and thereafter and localized to sperm tail. TMEM16E
−/−
sperm showed no apparent defect in morphology, beating, mitochondrial function, capacitation, or binding to zona pellucida. However, they showed reduced motility and inefficient fertilization of cumulus-free but zona-intact eggs in vitro. Our results suggest that TMEM16E may function as a phospholipid scramblase at inner membranes and that its defect affects sperm motility. |
| doi_str_mv | 10.1128/MCB.00919-15 |
| format | Article |
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2+
-dependent Cl
−
channels, while TMEM16C, -16D, -16F, -16G, and -16J support Ca
2+
-dependent phospholipid scrambling. Here, we show that TMEM16E carries a segment composed of 35 amino acids homologous to the scrambling domain in TMEM16F. When the corresponding segment of TMEM16A was replaced by this 35-amino-acid segment of TMEM16E, the chimeric molecule localized to the plasma membrane and supported Ca
2+
-dependent scrambling. We next established TMEM16E-deficient mice, which appeared to have normal skeletal muscle. However, fertility was decreased in the males. We found that TMEM16E was expressed in germ cells in early spermatogenesis and thereafter and localized to sperm tail. TMEM16E
−/−
sperm showed no apparent defect in morphology, beating, mitochondrial function, capacitation, or binding to zona pellucida. However, they showed reduced motility and inefficient fertilization of cumulus-free but zona-intact eggs in vitro. Our results suggest that TMEM16E may function as a phospholipid scramblase at inner membranes and that its defect affects sperm motility.</description><identifier>ISSN: 1098-5549</identifier><identifier>ISSN: 0270-7306</identifier><identifier>EISSN: 1098-5549</identifier><identifier>DOI: 10.1128/MCB.00919-15</identifier><identifier>PMID: 26667038</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>Amino Acid Sequence ; Animals ; Anoctamins ; Cell Line ; Chloride Channels - analysis ; Chloride Channels - genetics ; Chloride Channels - metabolism ; Female ; Fertilization ; Gene Deletion ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Molecular Sequence Data ; Mutation ; Protein Structure, Tertiary ; Sequence Alignment ; Sperm Motility ; Spermatozoa - cytology ; Spermatozoa - metabolism</subject><ispartof>Molecular and cellular biology, 2016-02, Vol.36 (4), p.645-659</ispartof><rights>Copyright © 2016, American Society for Microbiology 2016</rights><rights>Copyright © 2016, American Society for Microbiology. All Rights Reserved.</rights><rights>Copyright © 2016, American Society for Microbiology. All Rights Reserved. 2016 American Society for Microbiology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c498t-6c4c10833c1f99d923a95b85d931b00c017aa977106124c21f5b0e73dbcff2c83</citedby><cites>FETCH-LOGICAL-c498t-6c4c10833c1f99d923a95b85d931b00c017aa977106124c21f5b0e73dbcff2c83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751691/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751691/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26667038$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gyobu, Sayuri</creatorcontrib><creatorcontrib>Miyata, Haruhiko</creatorcontrib><creatorcontrib>Ikawa, Masahito</creatorcontrib><creatorcontrib>Yamazaki, Daiju</creatorcontrib><creatorcontrib>Takeshima, Hiroshi</creatorcontrib><creatorcontrib>Suzuki, Jun</creatorcontrib><creatorcontrib>Nagata, Shigekazu</creatorcontrib><title>A Role of TMEM16E Carrying a Scrambling Domain in Sperm Motility</title><title>Molecular and cellular biology</title><addtitle>Mol Cell Biol</addtitle><description>Transmembrane protein 16E (TMEM16E) belongs to the TMEM16 family of proteins that have 10 transmembrane regions and appears to localize intracellularly. Although TMEM16E mutations cause bone fragility and muscular dystrophy in humans, its biochemical function is unknown. In the TMEM16 family, TMEM16A and -16B serve as Ca
2+
-dependent Cl
−
channels, while TMEM16C, -16D, -16F, -16G, and -16J support Ca
2+
-dependent phospholipid scrambling. Here, we show that TMEM16E carries a segment composed of 35 amino acids homologous to the scrambling domain in TMEM16F. When the corresponding segment of TMEM16A was replaced by this 35-amino-acid segment of TMEM16E, the chimeric molecule localized to the plasma membrane and supported Ca
2+
-dependent scrambling. We next established TMEM16E-deficient mice, which appeared to have normal skeletal muscle. However, fertility was decreased in the males. We found that TMEM16E was expressed in germ cells in early spermatogenesis and thereafter and localized to sperm tail. TMEM16E
−/−
sperm showed no apparent defect in morphology, beating, mitochondrial function, capacitation, or binding to zona pellucida. However, they showed reduced motility and inefficient fertilization of cumulus-free but zona-intact eggs in vitro. Our results suggest that TMEM16E may function as a phospholipid scramblase at inner membranes and that its defect affects sperm motility.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Anoctamins</subject><subject>Cell Line</subject><subject>Chloride Channels - analysis</subject><subject>Chloride Channels - genetics</subject><subject>Chloride Channels - metabolism</subject><subject>Female</subject><subject>Fertilization</subject><subject>Gene Deletion</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Protein Structure, Tertiary</subject><subject>Sequence Alignment</subject><subject>Sperm Motility</subject><subject>Spermatozoa - cytology</subject><subject>Spermatozoa - metabolism</subject><issn>1098-5549</issn><issn>0270-7306</issn><issn>1098-5549</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkMtLxDAQh4MoPlZvnqVHD3bNNG3aXESt6wN2EXycQ5omGkmbNekq_e-t7ioKwsBMyMc3ww-hfcBjgKQ4npXnY4wZsBiyNbQNmBVxlqVs_de8hXZCeMEYU4bJJtpKKKU5JsU2Oj2L7pxVkdPRw2wyAzqJSuF9b9qnSET30oumsp-PC9cI00ZD3c-Vb6KZ64w1Xb-LNrSwQe2t-gg9Xk4eyut4ent1U55NY5myooupTCXgghAJmrGaJUSwrCqymhGoMJYYciFYngOmkKQyAZ1VWOWkrqTWiSzICJ0svfNF1ahaqrbzwvK5N43wPXfC8L8_rXnmT-6Np3kGlMEgOFwJvHtdqNDxxgSprBWtcovAIacJSaEAOqBHS1R6F4JX-mcNYP4ZOh9C51-hc8gG_OD3aT_wd8oDkC8B02rnG_HuvK15J3rrvPailSZw8q_6A1e9jWQ</recordid><startdate>20160201</startdate><enddate>20160201</enddate><creator>Gyobu, Sayuri</creator><creator>Miyata, Haruhiko</creator><creator>Ikawa, Masahito</creator><creator>Yamazaki, Daiju</creator><creator>Takeshima, Hiroshi</creator><creator>Suzuki, Jun</creator><creator>Nagata, Shigekazu</creator><general>Taylor & Francis</general><general>American Society for Microbiology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160201</creationdate><title>A Role of TMEM16E Carrying a Scrambling Domain in Sperm Motility</title><author>Gyobu, Sayuri ; Miyata, Haruhiko ; Ikawa, Masahito ; Yamazaki, Daiju ; Takeshima, Hiroshi ; Suzuki, Jun ; Nagata, Shigekazu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c498t-6c4c10833c1f99d923a95b85d931b00c017aa977106124c21f5b0e73dbcff2c83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Anoctamins</topic><topic>Cell Line</topic><topic>Chloride Channels - analysis</topic><topic>Chloride Channels - genetics</topic><topic>Chloride Channels - metabolism</topic><topic>Female</topic><topic>Fertilization</topic><topic>Gene Deletion</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Molecular Sequence Data</topic><topic>Mutation</topic><topic>Protein Structure, Tertiary</topic><topic>Sequence Alignment</topic><topic>Sperm Motility</topic><topic>Spermatozoa - cytology</topic><topic>Spermatozoa - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gyobu, Sayuri</creatorcontrib><creatorcontrib>Miyata, Haruhiko</creatorcontrib><creatorcontrib>Ikawa, Masahito</creatorcontrib><creatorcontrib>Yamazaki, Daiju</creatorcontrib><creatorcontrib>Takeshima, Hiroshi</creatorcontrib><creatorcontrib>Suzuki, Jun</creatorcontrib><creatorcontrib>Nagata, Shigekazu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular and cellular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gyobu, Sayuri</au><au>Miyata, Haruhiko</au><au>Ikawa, Masahito</au><au>Yamazaki, Daiju</au><au>Takeshima, Hiroshi</au><au>Suzuki, Jun</au><au>Nagata, Shigekazu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Role of TMEM16E Carrying a Scrambling Domain in Sperm Motility</atitle><jtitle>Molecular and cellular biology</jtitle><addtitle>Mol Cell Biol</addtitle><date>2016-02-01</date><risdate>2016</risdate><volume>36</volume><issue>4</issue><spage>645</spage><epage>659</epage><pages>645-659</pages><issn>1098-5549</issn><issn>0270-7306</issn><eissn>1098-5549</eissn><abstract>Transmembrane protein 16E (TMEM16E) belongs to the TMEM16 family of proteins that have 10 transmembrane regions and appears to localize intracellularly. Although TMEM16E mutations cause bone fragility and muscular dystrophy in humans, its biochemical function is unknown. In the TMEM16 family, TMEM16A and -16B serve as Ca
2+
-dependent Cl
−
channels, while TMEM16C, -16D, -16F, -16G, and -16J support Ca
2+
-dependent phospholipid scrambling. Here, we show that TMEM16E carries a segment composed of 35 amino acids homologous to the scrambling domain in TMEM16F. When the corresponding segment of TMEM16A was replaced by this 35-amino-acid segment of TMEM16E, the chimeric molecule localized to the plasma membrane and supported Ca
2+
-dependent scrambling. We next established TMEM16E-deficient mice, which appeared to have normal skeletal muscle. However, fertility was decreased in the males. We found that TMEM16E was expressed in germ cells in early spermatogenesis and thereafter and localized to sperm tail. TMEM16E
−/−
sperm showed no apparent defect in morphology, beating, mitochondrial function, capacitation, or binding to zona pellucida. However, they showed reduced motility and inefficient fertilization of cumulus-free but zona-intact eggs in vitro. Our results suggest that TMEM16E may function as a phospholipid scramblase at inner membranes and that its defect affects sperm motility.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>26667038</pmid><doi>10.1128/MCB.00919-15</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino Acid Sequence Animals Anoctamins Cell Line Chloride Channels - analysis Chloride Channels - genetics Chloride Channels - metabolism Female Fertilization Gene Deletion Male Mice Mice, Inbred C57BL Mice, Knockout Molecular Sequence Data Mutation Protein Structure, Tertiary Sequence Alignment Sperm Motility Spermatozoa - cytology Spermatozoa - metabolism |
| title | A Role of TMEM16E Carrying a Scrambling Domain in Sperm Motility |
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