ZFIN ID: ZDB-PUB-200422-183
GPCR-independent activation of G proteins promotes apical cell constriction in vivo
Marivin, A., Morozova, V., Walawalkar, I., Leyme, A., Kretov, D.A., Cifuentes, D., Dominguez, I., Garcia-Marcos, M.
Date: 2019
Source: The Journal of cell biology   218: 1743-1763 (Journal)
Registered Authors: Cifuentes, Daniel, Garcia-Marcos, Mikel
Keywords: none
MeSH Terms:
  • Actomyosin/metabolism
  • Animals
  • Cells, Cultured
  • Constriction
  • Embryo, Nonmammalian/cytology*
  • Embryo, Nonmammalian/metabolism
  • Guanine Nucleotide Exchange Factors/genetics
  • Guanine Nucleotide Exchange Factors/metabolism
  • Heterotrimeric GTP-Binding Proteins/genetics
  • Heterotrimeric GTP-Binding Proteins/metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins/genetics
  • Intracellular Signaling Peptides and Proteins/metabolism*
  • Microfilament Proteins/genetics
  • Microfilament Proteins/metabolism*
  • Morphogenesis*
  • Neural Plate/cytology*
  • Neural Plate/metabolism
  • Neurulation
  • Protein Interaction Domains and Motifs
  • Receptors, G-Protein-Coupled/genetics
  • Receptors, G-Protein-Coupled/metabolism*
  • Signal Transduction
  • Xenopus laevis/embryology
  • Xenopus laevis/physiology
  • Zebrafish/embryology
  • Zebrafish/physiology
PubMed: 30948426 Full text @ J. Cell Biol.
Heterotrimeric G proteins are signaling switches that control organismal morphogenesis across metazoans. In invertebrates, specific GPCRs instruct G proteins to promote collective apical cell constriction in the context of epithelial tissue morphogenesis. In contrast, tissue-specific factors that instruct G proteins during analogous processes in vertebrates are largely unknown. Here, we show that DAPLE, a non-GPCR protein linked to human neurodevelopmental disorders, is expressed specifically in the neural plate of Xenopus laevis embryos to trigger a G protein signaling pathway that promotes apical cell constriction during neurulation. DAPLE localizes to apical cell-cell junctions in the neuroepithelium, where it activates G protein signaling to drive actomyosin-dependent apical constriction and subsequent bending of the neural plate. This function is mediated by a Gα-binding-and-activating (GBA) motif that was acquired by DAPLE in vertebrates during evolution. These findings reveal that regulation of tissue remodeling during vertebrate development can be driven by an unconventional mechanism of heterotrimeric G protein activation that operates in lieu of GPCRs.