Back to Search Start Over

Sequence-dependent trafficking of GDE2, a GPI-specific phospholipase promoting neuronal differentiation

Authors :
Michiel van Veen
Fernando Salgado-Polo
Roy Baas
Daniela Leyton-Puig
Bram van den Broek
Wouter H. Moolenaar
Anastassis Perrakis
Elisa Matas-Rico
Publication Year :
2019
Publisher :
Cold Spring Harbor Laboratory, 2019.

Abstract

SummaryGDE2 is a six-transmembrane glycerophosphodiesterase with phospholipase D-like activity that cleaves select glycosylphosphatidylinositol (GPI)-anchored proteins and thereby influences biological signaling cascades. GDE2 promotes neuronal differentiation cell-autonomously through glypican cleavage and is a prognostic marker in neuroblastoma, while GDE2 deficiency causes progressive neurodegeneration in mice and developmental defects in zebrafish. However, the regulation of GDE2 remains unclear. Here we show that in undifferentiated neuronal cells, GDE2 undergoes constitutive internalization and traffics back along both fast and slow recycling routes, while a small percentage is sorted to late endosomes. GDE2 trafficking is dictated by distinctive C-terminal tail sequences that determine secretion, endocytosis and recycling preference, respectively, and thereby regulate GDE2 function both positively and negatively. Our study reveals the sequence determinants of GDE2 trafficking and surface localization, and provides insight into the control of GPI-anchored protein activities with potential implications for nervous system disorders associated with impaired trafficking and beyond.

Details

Language :
English
Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....b8a9b4c7c1c2102b97404d7a3e3b5e7c
Full Text :
https://doi.org/10.1101/532499