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...

Full description

Bibliographic Details
Main Authors: Seigo Usuki, Noriko Tamura, Tomohiro Tamura, Kunikazu Tanji, Daisuke Mikami, Katsuyuki Mukai, Yasuyuki Igarashi
Format: Article
Language:English
Published: MDPI AG 2019-04-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/20/9/2116
id doaj-adfe954e0dd74b41bf8dff0dbdbdb5d6
record_format Article
spelling 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 AT seigousuki neuriteoutgrowthandmorphologicalchangesinducedby8transunsaturationofsphingadienineinkcermolecularspecies
AT norikotamura neuriteoutgrowthandmorphologicalchangesinducedby8transunsaturationofsphingadienineinkcermolecularspecies
AT tomohirotamura neuriteoutgrowthandmorphologicalchangesinducedby8transunsaturationofsphingadienineinkcermolecularspecies
AT kunikazutanji neuriteoutgrowthandmorphologicalchangesinducedby8transunsaturationofsphingadienineinkcermolecularspecies
AT daisukemikami neuriteoutgrowthandmorphologicalchangesinducedby8transunsaturationofsphingadienineinkcermolecularspecies
AT katsuyukimukai neuriteoutgrowthandmorphologicalchangesinducedby8transunsaturationofsphingadienineinkcermolecularspecies
AT yasuyukiigarashi neuriteoutgrowthandmorphologicalchangesinducedby8transunsaturationofsphingadienineinkcermolecularspecies
_version_ 1725289857413021696