The retromer complex influences Wnt secretion by recycling wntless from endosomes to the trans-Golgi network.
Secreted Wnt proteins play essential roles in many biological processes during development and diseases. However, little is known about the mechanism(s) controlling Wnt secretion. Recent studies have identified Wntless (Wls) and the retromer complex as essential components involved in Wnt signaling. While Wls has been shown to be essential for Wnt secretion, the function(s) of the retromer complex in Wnt signaling is unknown. Here, we have examined a role of Vps35, an essential retromer subunit, in Wnt signaling in Drosophila and mammalian cells. We provide compelling evidence that the retromer complex is required for Wnt secretion. Importantly, Vps35 colocalizes in endosomes and interacts with Wls. Wls becomes unstable in the absence of retromer activity. Our findings link Wls and retromer functions in the same conserved Wnt secretion pathway. We propose that retromer influences Wnt secretion by recycling Wntless from endosomes to the trans-Golgi network (TGN).
Belenkaya
Tatyana Y
TY
Division of Developmental Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Wu
Yihui
Y
Tang
Xiaofang
X
Zhou
Bo
B
Cheng
Longqiu
L
Sharma
Yagya V
YV
Yan
Dong
D
Selva
Erica M
EM
Lin
Xinhua
X
D000818:Animals; D002462:Cell Membrane / Q000502:physiology*; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000502:physiology; D011992:Endosomes / Q000502:physiology*; D006706:Homeostasis; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000502:physiology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D021601:trans-Golgi Network / Q000502:physiology*
D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D033921:Vesicular Transport Proteins; C511046:Wls protein, Drosophila; D051153:Wnt Proteins