RRC ID 31983
Author Wang X, Page-McCaw A.
Title A matrix metalloproteinase mediates long-distance attenuation of stem cell proliferation.
Journal J. Cell Biol.
Abstract 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.
Volume 206(7)
Pages 923-36
Published 2014-9-29
DOI 10.1083/jcb.201403084
PII jcb.201403084
PMID 25267296
PMC PMC4178971
MeSH Adaptor Proteins, Signal Transducing / metabolism Animals Cell Communication Cell Line Cell Proliferation* Drosophila Proteins / metabolism Drosophila melanogaster / cytology Drosophila melanogaster / enzymology* Female Male Matrix Metalloproteinase 2 / physiology* Nuclear Proteins / metabolism Ovarian Follicle / cytology Protein Transport Proteolysis Stem Cell Niche Stem Cells / physiology* Wnt Signaling Pathway Wnt1 Protein / metabolism
IF 8.784
Times Cited 11
Drosophila 4889R-4 1794-1R-1