Glce regulates PC12 cell neuritogenesis induced by nerve growth factor through activating Smad/Id3 signaling

Neurodevelopment is orchestrated by a series of growth factor-heparan sulfate (HS) interactions which were involved in neuritogenesis. Glucuronic acid epimerase (Glce) is a critical enzyme involving in HS synthesis, which converts D-glucuronic acid (GlcA) to L-iduronic acid (IdoA). However, function of Glce in neuritogenesis is largely unknown. Here we showed that Glce depletion caused PC12 cell growth arrested and promoted the cell neuritogenesis and differentiation induced by nerve growth factor (NGF). PC12 cell growth was boosted by overexpression of Glce, and the neuritogenesis was impaired when Glce-depletion was rescued. Interestingly, overexpression of wild-type Glce with a Tyr168, Tyr222 to Ala168 and Ala222 mutation still led to enhanced PC12 cell growth and attenuated neuritogenesis triggered by Glcesilence. We further showed that Glce-depletion blocked Smad1/5/8 phosphorylation, however this signaling could be restored by Glce or the mutant at its active enzymatic site. In addition, the downstream effector of Smad1/5/8, Id3 was induced by Glce. Id3 silence inhibited PC12 cell growth and induced the cell neuritogenesis and differentiation. Besides, ectopic expression of Id3 partially rescued the phenotype caused by Glce silence. The results suggest that Glce plays a key role in PC12 cell growth and neuritogenesis through Smad/Id3 signaling.

Source: BJ Signal - February 5, 2014 Category: Biochemistry Authors: J Li, J Fang, Y Qin, W Liao, H Liu, Y Zhou, K Ding Tags: BJ Biomolecules Source Type: research