Neurite Outgrowth and Morphological Changes Induced by 8-trans Unsaturation of Sphingadienine in kCer Molecular Species
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 media...
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doaj-adfe954e0dd74b41bf8dff0dbdbdb5d62020-11-25T00:40:29ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-04-01209211610.3390/ijms20092116ijms20092116Neurite Outgrowth and Morphological Changes Induced by 8-trans Unsaturation of Sphingadienine in kCer Molecular SpeciesSeigo Usuki0Noriko Tamura1Tomohiro Tamura2Kunikazu Tanji3Daisuke Mikami4Katsuyuki Mukai5Yasuyuki Igarashi6Lipid Biofunction Section, Frontier Research Center for Advanced Material and Life Science, Faculty of Advanced Life Science, Hokkaido University, Sapporo 011-0021, JapanNational Institute of Advanced Industrial Science and Technology (AIST), Sapporo 061-8517, JapanNational Institute of Advanced Industrial Science and Technology (AIST), Sapporo 061-8517, JapanDepartment of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, JapanLipid Biofunction Section, Frontier Research Center for Advanced Material and Life Science, Faculty of Advanced Life Science, Hokkaido University, Sapporo 011-0021, JapanR&D Headquarters, Daicel Corporation, Tokyo 108-8230, JapanLipid Biofunction Section, Frontier Research Center for Advanced Material and Life Science, Faculty of Advanced Life Science, Hokkaido University, Sapporo 011-0021, JapanKonjac 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.https://www.mdpi.com/1422-0067/20/9/2116ceramidekonjacsemaphorin3Aneurite outgrowthneuropilin1endoglycoceramidasesphingadienine |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Seigo Usuki Noriko Tamura Tomohiro Tamura Kunikazu Tanji Daisuke Mikami Katsuyuki Mukai Yasuyuki Igarashi |
spellingShingle |
Seigo Usuki Noriko Tamura Tomohiro Tamura Kunikazu Tanji Daisuke Mikami Katsuyuki Mukai Yasuyuki Igarashi Neurite Outgrowth and Morphological Changes Induced by 8-trans Unsaturation of Sphingadienine in kCer Molecular Species International Journal of Molecular Sciences ceramide konjac semaphorin3A neurite outgrowth neuropilin1 endoglycoceramidase sphingadienine |
author_facet |
Seigo Usuki Noriko Tamura Tomohiro Tamura Kunikazu Tanji Daisuke Mikami Katsuyuki Mukai Yasuyuki Igarashi |
author_sort |
Seigo Usuki |
title |
Neurite Outgrowth and Morphological Changes Induced by 8-trans Unsaturation of Sphingadienine in kCer Molecular Species |
title_short |
Neurite Outgrowth and Morphological Changes Induced by 8-trans Unsaturation of Sphingadienine in kCer Molecular Species |
title_full |
Neurite Outgrowth and Morphological Changes Induced by 8-trans Unsaturation of Sphingadienine in kCer Molecular Species |
title_fullStr |
Neurite Outgrowth and Morphological Changes Induced by 8-trans Unsaturation of Sphingadienine in kCer Molecular Species |
title_full_unstemmed |
Neurite Outgrowth and Morphological Changes Induced by 8-trans Unsaturation of Sphingadienine in kCer Molecular Species |
title_sort |
neurite outgrowth and morphological changes induced by 8-trans unsaturation of sphingadienine in kcer molecular species |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-04-01 |
description |
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. |
topic |
ceramide konjac semaphorin3A neurite outgrowth neuropilin1 endoglycoceramidase sphingadienine |
url |
https://www.mdpi.com/1422-0067/20/9/2116 |
work_keys_str_mv |
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1725289857413021696 |