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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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Autores principales: Usuki, Seigo, Tamura, Noriko, Tamura, Tomohiro, Tanji, Kunikazu, Mikami, Daisuke, Mukai, Katsuyuki, Igarashi, Yasuyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540580/
https://www.ncbi.nlm.nih.gov/pubmed/31035716
http://dx.doi.org/10.3390/ijms20092116
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author Usuki, Seigo
Tamura, Noriko
Tamura, Tomohiro
Tanji, Kunikazu
Mikami, Daisuke
Mukai, Katsuyuki
Igarashi, Yasuyuki
author_facet Usuki, Seigo
Tamura, Noriko
Tamura, Tomohiro
Tanji, Kunikazu
Mikami, Daisuke
Mukai, Katsuyuki
Igarashi, Yasuyuki
author_sort Usuki, Seigo
collection PubMed
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.
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spelling pubmed-65405802019-06-04 Neurite Outgrowth and Morphological Changes Induced by 8-trans Unsaturation of Sphingadienine in kCer Molecular Species Usuki, Seigo Tamura, Noriko Tamura, Tomohiro Tanji, Kunikazu Mikami, Daisuke Mukai, Katsuyuki Igarashi, Yasuyuki Int J Mol Sci Article 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. MDPI 2019-04-29 /pmc/articles/PMC6540580/ /pubmed/31035716 http://dx.doi.org/10.3390/ijms20092116 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Usuki, Seigo
Tamura, Noriko
Tamura, Tomohiro
Tanji, Kunikazu
Mikami, Daisuke
Mukai, Katsuyuki
Igarashi, Yasuyuki
Neurite Outgrowth and Morphological Changes Induced by 8-trans Unsaturation of Sphingadienine in kCer Molecular Species
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540580/
https://www.ncbi.nlm.nih.gov/pubmed/31035716
http://dx.doi.org/10.3390/ijms20092116
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