A matrix metalloproteinase mediates long-distance attenuation of stem cell proliferation.
A matrix metalloproteinase mediates long-distance attenuation of stem cell proliferation.
复制标题
DOI：
10.1083/jcb.201403084
复制
发表时间：
2014-09-29
期刊：
影响因子：
--
通讯作者：
Page-McCaw A
中科院分区：
文献类型：
--
作者：
Wang X;Page-McCaw A
果蝇卵巢中Wingless的远程信号传导需要磷脂酰肌醇蛋白聚糖Dally样，并被细胞外金属蛋白酶Mmp 2的Dally样切割所拮抗。基于配体的信号传导可以加强相邻细胞之间以及相隔很远的细胞之间的通信。在果蝇卵巢中，Wingless（Wg）促进位于距离Wg源约50 µm或5个细胞直径的卵泡干细胞的增殖。Wg如何穿越这段距离尚不清楚。我们发现，这种远程信号需要分裂异常延迟（Dally）样（Dlp），磷脂酰肌醇蛋白聚糖已知的Wg配体的范围内的翼盘结合Wg。Dlp介导的Wg向卵泡干细胞的扩散受到细胞外蛋白酶Mmp 2的反对，Mmp 2在细胞培养物中切割Dlp，触发其重新定位，使得Dlp不再接触Wg蛋白。Mmp 2缺陷卵巢显示增加Wg分布，活性和干细胞增殖。Mmp 2蛋白在产生Wg的相同细胞中表达;因此，小生境细胞产生长距离干细胞增殖因子和其扩散的负调节因子。该系统可以允许对Wg信号传导到距源不同距离处的目标的空间控制。
Long-range signaling by Wingless in the Drosophila ovary requires the glypican Dally-like and is antagonized by Dally-like cleavage by the extracellular metalloproteinase Mmp2. Ligand-based signaling can potentiate communication between neighboring cells and between cells separated by large distances. In the Drosophila melanogaster ovary, Wingless (Wg) promotes proliferation of follicle stem cells located ∼50 µm or five cell diameters away from the Wg source. How Wg traverses this distance is unclear. We find that this long-range signaling requires Division abnormally delayed (Dally)-like (Dlp), a glypican known to extend the range of Wg ligand in the wing disc by binding Wg. Dlp-mediated spreading of Wg to follicle stem cells is opposed by the extracellular protease Mmp2, which cleaved Dlp in cell culture, triggering its relocalization such that Dlp no longer contacted Wg protein. Mmp2-deficient ovaries displayed increased Wg distribution, activity, and stem cell proliferation. Mmp2 protein is expressed in the same cells that produce Wg; thus, niche cells produce both a long-range stem cell proliferation factor and a negative regulator of its spreading. This system could allow for spatial control of Wg signaling to targets at different distances from the source.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.6
作者：
Desbordes, SC;Sanson, B
通讯作者：
Sanson, B
影响因子：
64.5
作者：
Belenkaya, TY;Han, C;Lin, XH
通讯作者：
Lin, XH
影响因子：
12.3
作者：
Filmus J;Capurro M;Rast J
通讯作者：
Rast J
影响因子：
5.3
作者：
Decock J;Thirkettle S;Wagstaff L;Edwards DR
通讯作者：
Edwards DR