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Open AccessArticle

Neurite Outgrowth and Morphological Changes Induced by 8-trans Unsaturation of Sphingadienine in kCer Molecular Species

1
Lipid Biofunction Section, Frontier Research Center for Advanced Material and Life Science, Faculty of Advanced Life Science, Hokkaido University, Sapporo 011-0021, Japan
2
National Institute of Advanced Industrial Science and Technology (AIST), Sapporo 061-8517, Japan
3
Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
4
R&D Headquarters, Daicel Corporation, Tokyo 108-8230, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(9), 2116; https://doi.org/10.3390/ijms20092116
Received: 28 March 2019 / Revised: 19 April 2019 / Accepted: 23 April 2019 / Published: 29 April 2019
(This article belongs to the Special Issue Ceramide)
Konjac ceramide (kCer), which consists of plant-type molecular species of characteristic shingoid bases and fatty acids, is prepared from konjac glucosylceramide GlcCer by chemoenzymatical deglucosylation. kCer activates the semaphorin 3A (Sema3A) signaling pathway, inducing collapsin response mediator protein 2 (CRMP2) phosphorylation. This results in neurite outgrowth inhibition and morphological changes in remaining long neurites in PC12 cells. Whether a specific molecular species of kCer can bind to the Sema3A receptor (Neuropilin1, Nrp1) and activate the Sema3A signaling pathway remains unknown. Here, we prepared kCer molecular species using endoglycoceramidase I-mediated deglucosylation and examined neurite outgrowth and phosphorylation of collapsin response mediator protein 2 in nerve growth factor (NGF)-primed cells. The 8-trans unsaturation of sphingadienine of kCer was essential for Sema3A-like signaling pathway activation. Conversely, 8-cis unsaturation of kCer molecular species had no effect on Sema3A-like activation, and neurite outgrowth inhibition resulted in remaining short neurites. In addition, α-hydroxylation of fatty acids was not associated with the Sema3A-like activity of the kCer molecular species. These results suggest that 8-trans or 8-cis isomerization of sphingadienine determines the specific interactions at the ligand-binding site of Nrp1. View Full-Text
Keywords: ceramide; konjac; semaphorin3A; neurite outgrowth; neuropilin1; endoglycoceramidase; sphingadienine ceramide; konjac; semaphorin3A; neurite outgrowth; neuropilin1; endoglycoceramidase; sphingadienine
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MDPI and ACS Style

Usuki, S.; Tamura, N.; Tamura, T.; Tanji, K.; Mikami, D.; Mukai, K.; Igarashi, Y. Neurite Outgrowth and Morphological Changes Induced by 8-trans Unsaturation of Sphingadienine in kCer Molecular Species. Int. J. Mol. Sci. 2019, 20, 2116.

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