Center for Regenerative Therapies Dresden (CRTD), TU Dresden, Tatzberg, Germany.
Nat Commun. 2011 Aug 2;2:415. doi: 10.1038/ncomms1426.
According to the stem cell niche synapse hypothesis postulated for the mammalian haematopoietic system, spatial specificity of niche signals is maximized by subcellularly restricting signalling to cadherin-based adherens junctions between individual niche and stem cells. However, such a synapse has never been observed directly, in part, because tools to detect active growth factor receptors with subcellular resolution were not available. Here we describe a novel fluorescence-based reporter that directly visualizes bone morphogenetic protein (BMP) receptor activation and show that in the Drosophila testis a BMP niche signal is transmitted preferentially at adherens junctions between hub and germline stem cells, resembling the proposed synapse organization. Ligand secretion involves the exocyst complex and the Rap activator Gef26, both of which are also required for Cadherin trafficking towards adherens junctions. We, therefore, propose that local generation of the BMP signal is achieved through shared use of the Cadherin transport machinery.
根据提出的哺乳动物造血系统干细胞生态位突触假说,通过将信号局限于单个生态位和干细胞之间基于钙黏蛋白的黏附连接的细胞内,最大限度地提高了生态位信号的空间特异性。然而,由于缺乏具有亚细胞分辨率的检测活性生长因子受体的工具,这种突触从未被直接观察到。在这里,我们描述了一种新的荧光报告器,可以直接可视化骨形态发生蛋白 (BMP) 受体的激活,并表明在果蝇睾丸中,BMP 生态位信号优先在枢纽和生殖干细胞之间的黏附连接处传递,类似于拟议的突触组织。配体分泌涉及外核小体复合物和 Rap 激活因子 Gef26,它们对于钙黏蛋白向黏附连接的运输也是必需的。因此,我们提出局部生成 BMP 信号是通过共享钙黏蛋白运输机制来实现的。