Stem-cell niche self-restricts the signaling range via receptor-ligand degradation

Abstract

Stem-cell niche signaling is short-range in nature, such that only stem cells but not their differentiating progeny experience self-renewing signals. At the apical tip of the Drosophila testes, 8 to 10 germline stem cells (GSCs) surround the hub, a cluster of somatic cells that function as the major component of the stem cell niche. We have shown that GSCs form microtubule-based nanotubes (MT-nanotubes), which project into the hub cells, serving as the platform for niche signal reception: the receptor Tkv expressed by GSCs localizes to the surface of MT-nanotubes, where it receives the hub-derived ligand Decapentaplegic (Dpp), ensuring the reception of the ligand specifically by stem cells but not by differentiating cells. Here we show that receptor (Tkv)-ligand (Dpp) interaction at the surface of MT-nanotubes serves a second purpose of dampening the niche signaling: we found that the receptor Tkv and the ligand Dpp are internalized into hub cells and are degraded in the hub cell lysosomes. Perturbation of hub lysosomal function or MT-nanotube formation leads to excess receptor retention within germ cells as well as excess Dpp that diffuses out of the hub, leading to ectopic activation of niche signal in differentiating germ cells. Our results demonstrate that MT-nanotubes plays dual roles in ensuring the short-range nature of the niche signaling by 1) providing exclusive interphase of the niche ligand-receptor interaction and 2) limiting the amount of available ligand-receptor via their degradation.