Boundary cells restrict dystroglycan trafficking to control basement membrane sliding during tissue remodeling
Shelly TH McClatchey,
Zheng Wang,
Lara M Linden,
Eric L Hastie,
Lin Wang,
Wanqing Shen,
Alan Chen,
Qiuyi Chi,
David R Sherwood
Affiliations
Shelly TH McClatchey
Department of Biology, Duke University, Durham, United States
Zheng Wang
Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Wuhan, China; Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Gastrointestinal Surgery, Union Hospital, Wuhan, China; Development and Molecular Oncology Laboratory, Union Hospital, Wuhan, China
Lara M Linden
Department of Biology, Duke University, Durham, United States
Eric L Hastie
Department of Biology, Duke University, Durham, United States
Lin Wang
Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Wuhan, China; Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Wanqing Shen
Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Wuhan, China; Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Alan Chen
Department of Biology, Duke University, Durham, United States
Qiuyi Chi
Department of Biology, Duke University, Durham, United States
Epithelial cells and their underlying basement membranes (BMs) slide along each other to renew epithelia, shape organs, and enlarge BM openings. How BM sliding is controlled, however, is poorly understood. Using genetic and live cell imaging approaches during uterine-vulval attachment in C. elegans, we have discovered that the invasive uterine anchor cell activates Notch signaling in neighboring uterine cells at the boundary of the BM gap through which it invades to promote BM sliding. Through an RNAi screen, we found that Notch activation upregulates expression of ctg-1, which encodes a Sec14-GOLD protein, a member of the Sec14 phosphatidylinositol-transfer protein superfamily that is implicated in vesicle trafficking. Through photobleaching, targeted knockdown, and cell-specific rescue, our results suggest that CTG-1 restricts BM adhesion receptor DGN-1 (dystroglycan) trafficking to the cell-BM interface, which promotes BM sliding. Together, these studies reveal a new morphogenetic signaling pathway that controls BM sliding to remodel tissues.
