TY - JOUR TI - The Sec14-like phosphatidylinositol transfer proteins Sec14l3/SEC14L2 act as GTPase proteins to mediate Wnt/Ca2+ signaling AU - Gong, Bo AU - Shen, Weimin AU - Xiao, Wanghua AU - Meng, Yaping AU - Meng, Anming AU - Jia, Shunji A2 - Zhang, Hong VL - 6 PY - 2017 DA - 2017/05/02 SP - e26362 C1 - eLife 2017;6:e26362 DO - 10.7554/eLife.26362 UR - https://doi.org/10.7554/eLife.26362 AB - 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. KW - Sec14l3/SEC14L2 KW - Wnt/Ca2+ KW - GTPase protein KW - cell movements KW - embryos JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -