Spermatid Head Elongation with Normal Nuclear Shaping Requires ADP-Ribosyltransferase PARP11 (ARTD11) in Mice
Spermatid Head Elongation with Normal Nuclear Shaping Requires ADP-Ribosyltransferase PARP11 (ARTD11) in Mice
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DOI：
10.1095/biolreprod.114.123661
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发表时间：
2015-03-01
影响因子：
3.6
通讯作者：
Meyer, Ralph G.
中科院分区：
文献类型：
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作者：
Meyer-Ficca, Mirella L.;Ihara, Motomasa;Meyer, Ralph G.
精子是高度分化的细胞，其特征在于其种特异性的核形状和高度浓缩的染色质。头部形状异常是畸形精子症的一种表现形式，会损害受精能力。本研究表明，聚（ADP-核糖）聚合酶-11（ARTD 11/PARP 11），ADP-核糖基转移酶（ARTD）家族的成员，在精子细胞进行核凝聚和分化的优先表达。Parp 11基因的缺失导致小鼠畸形精子症和雄性不育，这是由于形成了形状异常的受精能力低下的精子，尽管睾丸重量和精子计数正常。在亚细胞水平上，PARP 11缺陷的伸长精子细胞揭示了与异常核形状相关的核膜和染色质分离的结构缺陷，表明PARP 11在精子发生过程中与核膜稳定性和核重组的功能相关性。在体外，PARP 11表现出单（ADP-核糖基）化活性，具有ADP-核糖基化自身的能力。在转染的体细胞中，PARP 11与核孔组分如NUP 153共定位。N-末端WWE结构域中的氨基酸Y 77、Q86和R95以及催化结构域的存在对于PARP 11与核膜的共定位是必需的，但与NUP 153的共定位不需要蛋白质的催化活性。这项研究表明，PARP 11是一种新的酶，对精子头部的正确成形很重要，并确定它是一个潜在的因素参与特发性哺乳动物畸形精子症。
Sperm are highly differentiated cells characterized by their species-specific nuclear shapes and extremely condensed chromatin. Abnormal head shapes represent a form of teratozoospermia that can impair fertilization capacity. This study shows that poly(ADP-ribose) polymerase-11 (ARTD11/PARP11), a member of the ADP-ribosyltransferase (ARTD) family, is expressed preferentially in spermatids undergoing nuclear condensation and differentiation. Deletion of the Parp11 gene results in teratozoospermia and male infertility in mice due to the formation of abnormally shaped fertilization-incompetent sperm, despite normal testis weights and sperm counts. At the subcellular level, PARP11-deficient elongating spermatids reveal structural defects in the nuclear envelope and chromatin detachment associated with abnormal nuclear shaping, suggesting functional relevance of PARP11 for nuclear envelope stability and nuclear reorganization during spermiogenesis. In vitro, PARP11 exhibits mono(ADP-ribosyl)ation activity with the ability to ADP-ribosylate itself. In transfected somatic cells, PARP11 colocalizes with nuclear pore components, such as NUP153. Amino acids Y77, Q86, and R95 in the N-terminal WWE domain, as well as presence of the catalytic domain, are essential for colocalization of PARP11 with the nuclear envelope, but catalytic activity of the protein is not required for colocalization with NUP153. This study demonstrates that PARP11 is a novel enzyme important for proper sperm head shaping and identifies it as a potential factor involved in idiopathic mammalian teratozoospermia.