PUBLICATION
The Sec14-like phosphatidylinositol transfer proteins Sec14l3/SEC14L2 act as GTPase proteins to mediate Wnt/Ca2+ signaling.
- Authors
- Gong, B., Shen, W., Xiao, W., Meng, Y., Meng, A., Jia, S.
- ID
- ZDB-PUB-170504-14
- Date
- 2017
- Source
- eLIFE 6: (Journal)
- Registered Authors
- Gong, Bo, Jia, Shunji, Meng, Anming
- Keywords
- cell biology, developmental biology, stem cells, zebrafish
- MeSH Terms
-
- Animals
- Calcium Signaling*
- Carrier Proteins/metabolism*
- Cell Line
- Frizzled Receptors/metabolism
- GTP Phosphohydrolases/metabolism*
- Humans
- Lipoproteins/metabolism*
- Phospholipid Transfer Proteins/metabolism*
- Trans-Activators/metabolism*
- Type C Phospholipases/metabolism
- Wnt Signaling Pathway*
- Zebrafish
- PubMed
- 28463110 Full text @ Elife
Citation
Gong, B., Shen, W., Xiao, W., Meng, Y., Meng, A., Jia, S. (2017) The Sec14-like phosphatidylinositol transfer proteins Sec14l3/SEC14L2 act as GTPase proteins to mediate Wnt/Ca2+ signaling.. eLIFE. 6.
Abstract
The non-canonical Wnt/Ca2+ signaling pathway plays important roles in embryonic development, tissue formation and diseases. However, it is unclear how the Wnt ligand-stimulated, G protein-coupled receptor Frizzled activates phospholipases for calcium release. Here, we report that the zebrafish/human phosphatidylinositol transfer protein Sec14l3/SEC14L2 act as GTPase proteins to transduce Wnt signals from Frizzled to phospholipase C (PLC). Depletion of sec14l3 attenuates Wnt/Ca2+ responsive activity and causes convergent and extension (CE) defects in zebrafish embryos. Biochemical analyses in mammalian cells indicate that Sec14l3-GDP forms complex with Frizzled and Dishevelled; Wnt ligand binding of Frizzled induces translocation of Sec14l3 to the plasma membrane; and then Sec14l3-GTP binds to and activates phospholipase Cδ4a (Plcδ4a); subsequently, Plcδ4a initiates phosphatidylinositol-4,5-bisphosphate (PIP2) signaling, ultimately stimulating calcium release. Furthermore, Plcδ4a can act as a GTPase-activating protein to accelerate the hydrolysis of Sec14l3-bound GTP to GDP. Our data provide a new insight into GTPase protein-coupled Wnt/Ca2+ signaling transduction.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping