Transmembrane Protein GDE2 Induces Motor Neuron Differentiation in Vivo

Abstract

During neural development, coordinate regulation of cell-cycle exit and differentiation is essential for cell-fate specification, cell survival, and proper wiring of neuronal circuits. However, the molecules that direct these events remain poorly defined. In the developing spinal cord, the differentiation of motor neuron progenitors into postmitotic motor neurons is regulated by retinoid signaling. Here, we identify a retinoid-inducible gene, GDE2 (glycerophosphodiester phosphodiesterase 2), encoding a six-transmembrane protein that is necessary and sufficient to drive spinal motor neuron differentiation in vivo. A single amino acid mutation in the extracellular catalytic domain abolishes protein function. This reveals a critical role for glycerophosphodiester metabolism in motor neuron differentiation.

BM88/CEND1 coordinates cell cycle exit and differentiation of neuronal precursors

“…BM88 is sufficient to down-regulate Notch1 signaling, cause precocious and ectopic neurogenesis, and additionally induce ectopic generation of MNs in the VZ. Interestingly, glycerophosphodiester phosphodiestarase 2, which like BM88 is a retinoid-inducible neuronal membrane protein, generates a similar to BM88 phenotype by inducing MN generation in the chick spinal cord (22). The ability of BM88 to induce ectopic neurons within the VZ appears to be context dependent.…”

High NaCl- and urea-induced posttranslational modifications that increase glycerophosphocholine by inhibiting GDPD5 phosphodiesterase

“…2C). GDPD5 contains many predicted membranespanning regions (10,16). However, although mouse GDPD5-V5 is located in the region of the endoplasmic reticulum of HEK293 cells (6), chicken GDPD5-FLAG is located in the plasma membrane in chicken neurons and in HEK293 cells (12).…”

“…Bacterial GDPDs have a conserved catalytic site (11), which is present in GDPD5 (10). Because mutation of a crucial histidine in the putative site to alanine eliminates the effect of GDPD5 on neuronal differentiation, GDPD activity was deemed to be necessary (10). Using neuronal differentiation as the end point, the antioxidant scavenger peroxiredoxin (Prdx1) was found to activate GDPD5 by a thiol-redox-dependent reaction (12).…”

“…Retinoic acid, which signals neuronal differentiation, increases the expression of GDPD5 in motor neurons of chickens, and GDPD5 is necessary and sufficient for the neuronal differentiation (10). Bacterial GDPDs have a conserved catalytic site (11), which is present in GDPD5 (10). Because mutation of a crucial histidine in the putative site to alanine eliminates the effect of GDPD5 on neuronal differentiation, GDPD activity was deemed to be necessary (10).…”

“…Retinoic acid, which signals neuronal differentiation, increases the expression of GDPD5 in motor neurons of chickens, and GDPD5 is necessary and sufficient for the neuronal differentiation (10). Bacterial GDPDs have a conserved catalytic site (11), which is present in GDPD5 (10).…”