Mutations in twinstar, a Drosophila gene encoding a cofilin/ADF homologue, result in defects in centrosome migration and cytokinesis.
Mutations in twinstar, a Drosophila gene encoding a cofilin/ADF homologue, result in defects in centrosome migration and cytokinesis.
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DOI：
10.1083/jcb.131.5.1243
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发表时间：
1995-12
期刊：
影响因子：
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通讯作者：
Goldberg ML
中科院分区：
文献类型：
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作者：
Gunsalus KC;Bonaccorsi S;Williams E;Verni F;Gatti M;Goldberg ML
我们描述了双星（tsr）的表型和分子特征，双星是黑腹果蝇的一个重要基因。tsr的两个p元素诱导等位基因（tsr1和tsr2）导致了后期幼虫或蛹的死亡。对这些突变体活跃分裂组织的细胞学检查显示有丝分裂细胞（成神经细胞幼虫）和减数分裂细胞（睾丸幼虫）的细胞分裂缺陷。此外，突变的精母细胞在减数分裂的前中期和前中期都表现出加速迁移和分离的缺陷。我们克隆了受这些突变影响的基因，并表明它编码cofilin/ADF小肌动蛋白切断蛋白家族中的一个17-kD蛋白。此前，Edwards等人（1994）描述了该基因的cDNA。Northern分析表明，tsr基因在整个发育过程中表达，tsr1和tsr2等位基因是次型，tsr mRNA水平降低。这些发现促使我们研究雄性减数分裂期间肌动蛋白的行为，以可视化双星蛋白活性降低对体内肌动蛋白动力学的影响。引人注目的是，这两种突变体都表现出F-肌动蛋白的异常积累。大的肌动蛋白聚集体在成熟的初级精母细胞中与中心体相关。随后，在两种减数分裂的ana/末期，与野生型相比，在收缩环形成部位出现异常大且畸形的结构，并且在末期结束时无法拆卸。我们讨论这些结果在可能的作用方面，以肌动蛋白为基础的细胞骨架在中心体运动和细胞质分裂。
We describe the phenotypic and molecular characterization of twinstar (tsr), an essential gene in Drosophila melanogaster. Two P-element induced alleles of tsr (tsr1 and tsr2) result in late larval or pupal lethality. Cytological examination of actively dividing tissues in these mutants reveals defects in cytokinesis in both mitotic (larval neuroblast) and meiotic (larval testis) cells. In addition, mutant spermatocytes show defects in aster migration and separation during prophase/prometaphase of both meiotic divisions. We have cloned the gene affected by these mutations and shown that it codes for a 17-kD protein in the cofilin/ADF family of small actin severing proteins. A cDNA for this gene has previously been described by Edwards et al. (1994). Northern analysis shows that the tsr gene is expressed throughout development, and that the tsr1 and tsr2 alleles are hypomorphs that accumulate decreased levels of tsr mRNA. These findings prompted us to examine actin behavior during male meiosis to visualize the effects of decreased twinstar protein activity on actin dynamics in vivo. Strikingly, both mutants exhibit abnormal accumulations of F- actin. Large actin aggregates are seen in association with centrosomes in mature primary spermatocytes. Later, during ana/telophase of both meiotic divisions, aberrantly large and misshaped structures appear at the site of contractile ring formation and fail to disassemble at the end of telophase, in contrast with wild-type. We discuss these results in terms of possible roles of the actin-based cytoskeleton in centrosome movement and in cytokinesis.