RT Journal Article
SR Electronic
T1 Visualizing Wnt secretion from Endoplasmic Reticulum to Filopodia
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 271684
DO 10.1101/271684
A1 Naushad Moti
A1 Jia Yu
A1 Gaelle Boncompain
A1 Franck Perez
A1 David M Virshup
YR 2018
UL http://biorxiv.org/content/early/2018/04/14/271684.abstract
AB Wnts are a family of secreted cysteine-rich palmitoleated glycoproteins that play a key role in cell to cell communications during development and in regulation of stem cell compartments in adults. Dysregulation of Wnt signaling is implicated in multiple pathological processes. Wnt receptors, downstream signaling cascades and target pathways have been extensively studied while less is known about how Wnts are secreted and move from producing cells to receiving cells. We used the synchronization system called Retention Using Selective Hook (RUSH) to study Wnt trafficking from endoplasmic reticulum to Golgi and then to plasma membrane and filopodia in real time. Consistent with prior studies, inhibition of porcupine (PORCN) or knockout of Wntless (WLS) blocked Wnt exit from the ER. Indeed, WLS was rate-limiting for Wnt ER exit. Wnt-containing vesicles paused at sub-cortical regions of the plasma membrane before exiting the cell. Wnt-containing vesicles were transported to adjacent cells associated with filopodia. Increasing the number of filopodia by expression of LGR5 in the producing cell increased the ability of a cell to send a Wnt signal. The RUSH system is a useful tool to characterize the Wnt secretory pathway and will facilitate the identification and function of additional regulators of Wnt protein secretion and filopodial transport.