A Protein Disulfide Isomerase Controls Neuronal Migration through Regulation of Wnt Secretion

Abstract

Highlights d PDI-1, a protein disulfide isomerase, regulates neuron migration d PDI-1 functions in EGL-20/Wnt-producing cells to control neuron migration d Protein disulfide isomerases are evolutionarily conserved regulators of Wnt secretion

Computational modeling and analysis of the morphogenetic domain signaling networks regulating C. elegans embryogenesis

“…Cell-to-cell signaling network. Cells signal to each other by direct contacts [15] or by the release of a substance from one cell that is taken up by another cell [47] . The fate and behavior of the cell is determined through the communication with its neighboring cells.…”

“…The morphogenetic domain signaling network is regulated by a population of cells that secret the molecules collectively to form the morphogen gradients that can diffuse over distance for directing cell communications and collective behaviors. The gradient can be interpreted by cells in a position dependent and level sensitive manner in regulating cell fate decision and behavior output [47] , [52] , [53] . The combinatorial code of the morphogen gradients played important roles in inducing complex tissue pattern formation in embryo development.…”

Roles of Protein Disulfide Isomerase in Breast Cancer

“…So, the knockdown of PDI in MCF-7 cells results in a significant increase in the ERβ/ERα ratio, possibly providing the beneficial effect of cancer prevention. Recently, PDI has been found to be vital for Wnt3a secretion and for the regulation of Wnt signaling, which is mainly involved in the processes of breast cancer proliferation and metastasis [83,84].…”

P5A ATPase controls ER translocation of Wnt in neuronal migration

“…WNT1 secretion assay in HEK293FT or SH-SY5Y cells WNT1 secretion assay were performed as described (Torpe et al, 2019). Control and ATP13A1 KO cells were cultured overnight in DMEM containing serum and L-glutamine.…”

“…QL migrates posteriorly, differentiating into PQR, PVM, and SDQL neurons (Figures 1A and 1B), whereas QR migrates anteriorly, producing AQR, AVM, and SDQR neurons. Q neuroblast migration is activated by EGL-20/Wnt proteins secreted posteriorly (Coudreuse et al, 2006), a process mediated through the endocytosis of Wnt-transport factor MIG-14/Wls by Retromer complex as well as proper folding by protein disulfide isomerase (PDI-1) (Coudreuse et al, 2006;Pan et al, 2008;Torpe et al, 2019;Yang et al, 2008). Binding of EGL-20/Wnt to the Frizzled receptors LIN-17 and MIG-1 in the QL leads to the activation of the canonical Wnt signaling with BAR-1/b-catenin stabilization and nuclear localization (Harris et al, 1996;Maloof et al, 1999;Sawa et al, 1996), which induces the transcription of target genes, including mab-5 (Harris et al, 1996;Salser and Kenyon, 1992;Whangbo and Kenyon, 1999).…”