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

2019 ◽  
Vol 20 (9) ◽  
pp. 2116 ◽  
Author(s):  
Seigo Usuki ◽  
Noriko Tamura ◽  
Tomohiro Tamura ◽  
Kunikazu Tanji ◽  
Daisuke Mikami ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Neurite Outgrowth ◽  
Signaling Pathway ◽  
Molecular Species ◽  
Morphological Changes ◽  
Semaphorin 3A ◽  
Collapsin Response Mediator Protein ◽  
Trans Unsaturation ◽  
Pathway Activation ◽  
Mediator Protein

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.

Collapsin response-mediator protein 5 (CRMP5) phosphorylation at threonine 516 regulates neurite outgrowth inhibition

2014 ◽  
Vol 40 (7) ◽  
pp. 3010-3020 ◽  
Author(s):  
Sébastien Brot ◽  
Hinda Smaoune ◽  
Mina Youssef-Issa ◽  
Céline Malleval ◽  
Claire Benetollo ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Collapsin Response Mediator Protein ◽  
Mediator Protein

Phosphorylation of Collapsin Response Mediator Protein 1 (CRMP1) at Tyrosine 504 residue regulates Semaphorin 3A‐induced cortical dendritic growth

2021 ◽  
Author(s):  
Takeshi Kawashima ◽  
Aoi Jitsuki‐Takahashi ◽  
Kohtaro Takizawa ◽  
Susumu Jitsuki ◽  
Takuya Takahashi ◽  
...  
Keyword(s):  
Dendritic Growth ◽  
Semaphorin 3A ◽  
Collapsin Response Mediator Protein ◽  
Mediator Protein

Role of collapsin response mediator protein-2 in neurite outgrowth of PC12 cells

Neuroreport ◽  
2010 ◽  
Vol 21 (9) ◽  
pp. 641-645 ◽  
Author(s):  
Kaya Bork ◽  
Yvonne Karbe ◽  
Juliane Pollscheit ◽  
Nicole Glaubitz ◽  
Sabine Nöhring ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Collapsin Response Mediator Protein ◽  
Mediator Protein

scholarly journals CRMP4-mediated fornix development involves semaphorin-3E signaling pathway

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Benoît Boulan ◽  
Charlotte Ravanello ◽  
Amandine Peyrel ◽  
Christophe Bosc ◽  
Christian Delphin ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cognitive Abilities ◽  
Axonal Guidance ◽  
Psychiatric Diseases ◽  
Receptor Complex ◽  
Axonal Pathfinding ◽  
Collapsin Response Mediator Protein ◽  
Guidance Cue ◽  
Mediator Protein ◽  
Growth Promoting

Neurodevelopmental axonal pathfinding plays a central role in correct brain wiring and subsequent cognitive abilities. Within the growth cone, various intracellular effectors transduce axonal guidance signals by remodeling the cytoskeleton. Semaphorin-3E (Sema3E) is a guidance cue implicated in development of the fornix, a neuronal tract connecting the hippocampus to the hypothalamus. Microtubule-Associated Protein 6 (MAP6) has been shown to be involved in the Sema3E growth-promoting signaling pathway. In this study, we identified the Collapsin Response Mediator Protein 4 (CRMP4) as a MAP6 partner and a crucial effector in Sema3E growth-promoting activity. CRMP4-KO mice displayed abnormal fornix development reminiscent of that observed in Sema3E-KO mice. CRMP4 was shown to interact with the Sema3E tripartite receptor complex within Detergent-Resistant Membrane (DRM) domains, and DRM domain integrity was required to transduce Sema3E signaling through the Akt/GSK3 pathway. Finally, we showed that the cytoskeleton-binding domain of CRMP4 is required for Sema3E's growth-promoting activity, suggesting that CRMP4 plays a role at the interface between Sema3E receptors, located in DRM domains, and the cytoskeleton network. As the fornix is affected in many psychiatric diseases, such as schizophrenia, our results provide new insights to better understand the neurodevelopmental components of these diseases.

Spastin Interacts with CRMP2 to Regulate Neurite Outgrowth by Controlling Microtubule Dynamics through Phosphorylation Modifications

2020 ◽  
Vol 19 ◽  
Author(s):  
Sumei Li ◽  
Jifeng Zhang ◽  
Jiaqi Zhang ◽  
Jiong Li ◽  
Longfei Cheng ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Hippocampal Neurons ◽  
Neuronal Development ◽  
Phosphorylation Site ◽  
Microtubule Dynamics ◽  
Microtubule Assembly ◽  
C Terminus ◽  
Mediator Protein ◽  
Branch Formation

Aims: Our work aims to revealing the underlying microtubule mechanism of neurites outgrowth during neuronal development, and also proposes a feasible intervention pathway for reconstructing neural network connections after nerve injury. Background: Microtubule polymerization and severing are the basis for the neurite outgrowth and branch formation. Collapsin response mediator protein 2 (CRMP2) regulates axonal growth and branching as a binding partner of the tubulin heterodimer to promote microtubule assembly. And spastin participates in the growth and regeneration of neurites by severing microtubules into small segments. However, how CRMP2 and spastin cooperate to regulate neurite outgrowth by controlling the microtubule dynamics needs to be elucidated. Objective: To explore whether neurite outgrowth was mediated by coordination of CRMP2 and spastin. Method: Hippocampal neurons were cultured in vitro in 24-well culture plates for 4 days before being used to perform the transfection. Calcium phosphate was used to transfect the CRMP2 and spastin constructs and their control into the neurons. An interaction between CRMP2 and spastin was examined by using pull down, CoIP and immunofluorescence colocalization assays. And immunostaining was also performed to determine the morphology of neurites. Result: We first demonstrated that CRMP2 interacted with spastin to promote the neurite outgrowth and branch formation. Furthermore, our results identified that phosphorylation modification failed to alter the binding affinities of CRMP2 for spastin, but inhibited their binding to microtubules. CRMP2 interacted with the MTBD domain of spastin via its C-terminus, and blocking the binding sites of them inhibited the outgrowth and branch formation of neurites. In addition, we confirmed one phosphorylation site S210 at spastin in hippocampal neurons and phosphorylation spastin at site S210 promoted the neurite outgrowth but not branch formation by remodeling microtubules. Conclusion: Taken together, our data demonstrated that the interaction of CRMP2 and spastin is required for neurite outgrowth and branch formation and their interaction is not regulated by their phosphorylation.

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