The Ancient and Evolved Mouse Sperm-Associated Antigen 6 Genes Have Different Biologic Functions In Vivo.
The Ancient and Evolved Mouse Sperm-Associated Antigen 6 Genes Have Different Biologic Functions In Vivo.
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DOI：
10.3390/cells11030336
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发表时间：
2022-01-20
期刊：
影响因子：
6
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Yap YT;Li W;Zhou Q;Haj-Diab S;Chowdhury DD;Vaishnav A;Harding P;Williams DC Jr;Edwards BF;Strauss JF 3rd;Zhang Z
精子相关抗原6(SPAG6)是衣藻PF16的哺乳动物同源基因，衣藻PF16是一种参与鞭毛运动的轴丝中央对蛋白。在老鼠身上，已经发现了两个Spag6基因。位于老鼠2号染色体上的祖先基因被命名为Spag6。一种最初被称为Spag6的相关基因，定位于小鼠的16号染色体，是从古老的Spag6基因进化而来的。它已被重新命名为Spag6-Like(Spag61)。Spag6编码一个1.6kb的转录本，由11个外显子组成，而Spag61编码一个2.4kb的转录本，它在3‘端包含一个额外的非编码外显子，以及Spag6中发现的11个外显子。这两个Spag6基因在核苷酸和氨基酸序列上有很高的相似性。与广泛表达的Spag61mRNA不同，Spag6mRNA的表达仅限于少数组织，包括睾丸和大脑。在转基因哺乳动物细胞中，SPAG6/GFP定位于微管，与SPAG6L定位相似。之前已经生成了一个全局Spag61基因敲除小鼠模型。除了调节纤毛节拍外，SPAG6L还具有许多意想不到的功能，包括调节纤毛发生/精子发生、听力和免疫突触等。为了研究古老的Spag6基因的作用，我们对全球Spag6基因敲除小鼠进行了表型鉴定。所有纯合子突变小鼠大体正常，雄性和雌性的生育能力都没有受到影响。纯合子男性的精子参数正常，包括精子数量、活动率和形态。睾丸组织学检查显示生精功能正常。在Spag6基因敲除小鼠中，包括SPAG16L在内的部分SPAG6L结合伙伴的睾丸蛋白表达水平没有变化，尽管Spag6L基因敲除小鼠的SPAG16L水平显著降低。对这两种SPAG6蛋白的结构分析表明，它们的折叠非常相似，但有几个氨基酸存在差异，其中许多氨基酸是暴露在溶剂中的。这些差异赋予了这两种蛋白质不同的功能特征，尽管它们都有八个介导蛋白质-蛋白质相互作用的螳螂重复序列。我们的研究表明，SPAG6和SPAG6L在体内具有不同的功能，其中进化的SPAG6L蛋白更重要。由于这两个蛋白质有一些重叠的结合伙伴，SPAG6可能具有尚未确定的功能。
Sperm-associated antigen 6 (SPAG6) is the mammalian orthologue of Chlamydomonas PF16, an axonemal central pair protein involved in flagellar motility. In mice, two Spag6 genes have been identified. The ancestral gene, on mouse chromosome 2, is named Spag6. A related gene originally called Spag6, localized on mouse chromosome 16, evolved from the ancient Spag6 gene. It has been renamed Spag6-like (Spag6l). Spag6 encodes a 1.6 kb transcript consisting of 11 exons, while Spag6l encodes a 2.4 kb transcript which contains an additional non-coding exon in the 3′-end as well as the 11 exons found in Spag6. The two Spag6 genes share high similarities in their nucleotide and amino acid sequences. Unlike Spag6l mRNA, which is widely expressed, Spag6 mRNA expression is limited to a smaller number of tissues, including the testis and brain. In transfected mammalian cells, SPAG6/GFP is localized on microtubules, a similar localization as SPAG6L. A global Spag6l knockout mouse model was generated previously. In addition to a role in modulating the ciliary beat, SPAG6L has many unexpected functions, including roles in the regulation of ciliogenesis/spermatogenesis, hearing, and the immunological synapse, among others. To investigate the role of the ancient Spag6 gene, we phenotyped global Spag6 knockout mice. All homozygous mutant mice were grossly normal, and fertility was not affected in both males and females. The homozygous males had normal sperm parameters, including sperm number, motility, and morphology. Examination of testis histology revealed normal spermatogenesis. Testicular protein expression levels of selected SPAG6L binding partners, including SPAG16L, were not changed in the Spag6 knockout mice, even though the SPAG16L level was significantly reduced in the Spag6l knockout mice. Structural analysis of the two SPAG6 proteins shows that both adopt very similar folds, with differences in a few amino acids, many of which are solvent-exposed. These differences endow the two proteins with different functional characteristics, even though both have eight armadillo repeats that mediate protein–protein interaction. Our studies suggest that SPAG6 and SPAG6L have different functions in vivo, with the evolved SPAG6L protein being more important. Since the two proteins have some overlapping binding partners, SPAG6 could have functions that are yet to be identified.
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影响因子：
4.5
作者：
Gust, Kurt A.;Lotufo, Guilherme R.;Chappell, Pornsawan
通讯作者：
Chappell, Pornsawan
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
精子相关抗原 6 (SPAG6) 调节成纤维细胞生长、形态、迁移和纤毛发生
影响因子：
4.6
作者：
Li W;Mukherjee A;Wu J;Zhang L;Teves ME;Li H;Nambiar S;Henderson SC;Horwitz AR;Strauss JF III;Fang X;Zhang Z
通讯作者：
Zhang Z
影响因子：
3.7
作者：
Kitchen MO;Bryan RT;Haworth KE;Emes RD;Luscombe C;Gommersall L;Cheng KK;Zeegers MP;James ND;Devall AJ;Fryer AA;Farrell WE
通讯作者：
Farrell WE
影响因子：
4.4
作者：
Jarrell ZR;Ahammad MU;Sweeney K;Wilson JL;Benson AP
通讯作者：
Benson AP