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2014 ; 243
(9
): 1095-105
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Concentration-dependent effects of WNTLESS on WNT1/3A signaling
#MMPMID24866848
Galli LM
; Szabo LA
; Li L
; Htaik YM
; Onguka O
; Burrus LW
Dev Dyn
2014[Sep]; 243
(9
): 1095-105
PMID24866848
show ga
BACKGROUND: WNTLESS (WLS) is a multi-transmembrane protein that transports Wnt
ligands from the Golgi to the cell surface. Although WLS loss-of-function
experiments in the developing central nervous system reveal phenotypes consistent
with defects in WNT1 and WNT3A signaling, data from complementary
gain-of-function experiments have not yet been reported. Here, we report the
phenotypic consequences of WLS overexpression in cultured cells and in the
developing chick spinal cord. RESULTS: Overexpression of small amounts of WLS
along with either WNT1 or WNT3A promotes the Wnt/?-catenin pathway in HEK293T
cells, while overexpression of higher levels of WLS inhibits the Wnt/?-catenin
pathway in these cells. Similarly, overexpressed WLS inhibits the Wnt/?-catenin
pathway in the developing spinal cord, as assessed by cell proliferation and
specification. These effects appear to be Wnt-specific as overexpression of WLS
inhibits the expression of FZD10, a target of ?-catenin-dependent transcription.
CONCLUSIONS: Our results show that overexpression of WLS inhibits Wnt/?-catenin
signaling in the spinal cord. As the activation of the Wnt/?-catenin pathway in
the spinal cord requires WNT1 or WNT3A, our results are consistent with a model
in which the relative concentration of WLS to Wnt regulates WNT1/3A signaling in
the developing spinal cord.
|Animals
[MESH]
|Cell Proliferation
[MESH]
|Chick Embryo
[MESH]
|HEK293 Cells
[MESH]
|Humans
[MESH]
|Intracellular Signaling Peptides and Proteins/*genetics/metabolism
[MESH]