Qian Yue, Ng Chun L, Schulz Cordula
(a)University of Georgia, Department of Cellular Biology, Athens, GA 30602, USA; Ripon College, Department of Biology, Ripon, WI 54971, USA.
(a)University of Georgia, Department of Cellular Biology, Athens, GA 30602, USA.
Dev Biol. 2015 Feb 1;398(1):68-79. doi: 10.1016/j.ydbio.2014.11.014. Epub 2014 Nov 24.
Stem cells and their daughters are often associated with and depend on cues from their cellular microenvironment. In Drosophila testes, each Germline Stem Cell (GSC) contacts apical hub cells and is enclosed by cytoplasmic extensions from two Cyst Stem Cells (CySCs). Each GSC daughter becomes enclosed by cytoplasmic extensions from two CySC daughters, called cyst cells. CySC fate depends on an Unpaired (Upd) signal from the hub cells, which activates the Janus Kinase and Signal Transducer and Activator of Transcription (Jak/STAT) pathway in the stem cells. Germline enclosure depends on Epidermal Growth Factor (EGF) signals from the germline to the somatic support cells. Expression of RNA-hairpins against subunits of the COnstitutively Photomorphogenic-9- (COP9-) signalosome (CSN) in somatic support cells disrupted germline enclosure. Furthermore, CSN-depleted somatic support cells in the CySC position next to the hub had reduced levels of the Jak/STAT effectors Zinc finger homeotic-1 (Zfh-1) and Chronologically inappropriate morphogenesis (Chinmo). Knockdown of CSN in the somatic support cells does not disrupt EGF and Upd signal transduction as downstream signal transducers, phosphorylated STAT (pSTAT) and phosphorylated Mitogen Activated Protein Kinase (pMAPK), were still localized to the somatic support cell nuclei. The CSN modifies fully formed Cullin RING ubiquitin ligase (CRL) complexes to regulate selective proteolysis. Reducing cullin2 (cul2) from the somatic support cells disrupted germline enclosure, while reducing cullin1 (cul1) from the somatic support cells led to a low level of Chinmo. We propose that different CRLs enable the responses of somatic support cells to Upd and EGF.
干细胞及其子代细胞通常与细胞微环境中的信号相关联并依赖于这些信号。在果蝇睾丸中，每个生殖系干细胞（GSC）与顶端枢纽细胞接触，并被两个包囊干细胞（CySC）的细胞质延伸所包围。每个GSC子代细胞被两个CySC子代细胞（称为包囊细胞）的细胞质延伸所包围。CySC的命运取决于来自枢纽细胞的未配对（Upd）信号，该信号激活干细胞中的Janus激酶和信号转导及转录激活因子（Jak/STAT）途径。生殖系的包被取决于从生殖系到体细胞支持细胞的表皮生长因子（EGF）信号。在体细胞支持细胞中表达针对组成型光形态建成-9-（COP9-）信号体（CSN）亚基的RNA发夹会破坏生殖系的包被。此外，紧邻枢纽的CySC位置中CSN缺失的体细胞支持细胞中，Jak/STAT效应器锌指同源异型-1（Zfh-1）和时间上不适当的形态发生（Chinmo）的水平降低。在体细胞支持细胞中敲低CSN不会破坏EGF和Upd信号转导，因为下游信号转导器磷酸化的STAT（pSTAT）和磷酸化的丝裂原活化蛋白激酶（pMAPK）仍定位于体细胞支持细胞核中。CSN修饰完全形成的Cullin RING泛素连接酶（CRL）复合物以调节选择性蛋白水解。从体细胞支持细胞中减少cullin2（cul2）会破坏生殖系的包被，而从体细胞支持细胞中减少cullin1（cul1）会导致Chinmo水平降低。我们提出不同的CRL使体细胞支持细胞能够对Upd和EGF作出反应。
