Eikenes Åsmund Husabø, Malerød Lene, Lie-Jensen Anette, Sem Wegner Catherine, Brech Andreas, Liestøl Knut, Stenmark Harald, Haglund Kaisa
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, Oslo N-0379, Norway Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, Oslo N-0379, Norway.
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, Oslo N-0379, Norway Department of Informatics, University of Oslo, Oslo N-0316, Norway.
Development. 2015 Dec 1;142(23):4107-18. doi: 10.1242/dev.124370.
In many organisms, germ cells develop as cysts in which cells are interconnected via ring canals (RCs) as a result of incomplete cytokinesis. However, the molecular mechanisms of incomplete cytokinesis remain poorly understood. Here, we address the role of tyrosine phosphorylation of RCs in the Drosophila male germline. We uncover a hierarchy of tyrosine phosphorylation within germline cysts that positively correlates with RC age. The kinase Src64 is responsible for mediating RC tyrosine phosphorylation, and loss of Src64 causes a reduction in RC diameter within germline cysts. Mechanistically, we show that Src64 controls an actin network around the RCs that depends on Abl and the Rac/SCAR/Arp2/3 pathway. The actin network around RCs is required for correct RC diameter in cysts of developing germ cells. We also identify that Src64 is required for proper germ cell differentiation in the Drosophila male germline independent of its role in RC regulation. In summary, we report that Src64 controls actin dynamics to mediate proper RC formation during incomplete cytokinesis during germline cyst development in vivo.
在许多生物体中,生殖细胞以囊肿的形式发育,其中细胞由于不完全胞质分裂而通过环管(RCs)相互连接。然而,不完全胞质分裂的分子机制仍知之甚少。在这里,我们探讨了果蝇雄性生殖系中RCs酪氨酸磷酸化的作用。我们发现生殖系囊肿内酪氨酸磷酸化存在一个等级体系,它与RC的年龄呈正相关。激酶Src64负责介导RC酪氨酸磷酸化,Src64的缺失会导致生殖系囊肿内RC直径减小。从机制上讲,我们表明Src64控制RC周围的肌动蛋白网络,该网络依赖于Abl以及Rac/SCAR/Arp2/3途径。发育中的生殖细胞囊肿中正确的RC直径需要RC周围的肌动蛋白网络。我们还发现,Src64在果蝇雄性生殖系中对于适当的生殖细胞分化是必需的,这与其在RC调节中的作用无关。总之,我们报告Src64控制肌动蛋白动力学,以在体内生殖系囊肿发育过程中的不完全胞质分裂期间介导适当的RC形成。