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

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.

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

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.

scholarly journals Spastin interacts with CRMP5 to promote spindle organization in mouse oocytes by severing microtubules

Zygote ◽  
2021 ◽  
pp. 1-12
Author(s):  
Zhen Jin ◽  
Hua-Feng Shou ◽  
Jin-Wei Liu ◽  
Shan-Shan Jiang ◽  
Yan Shen ◽  
...  
Keyword(s):  
Developmental Disorders ◽  
Spindle Microtubule ◽  
Collapsin Response Mediator Protein ◽  
Microtubule Severing ◽  
Structural Support ◽  
Mediator Protein ◽  
Spindle Microtubules ◽  
Transportation Routes ◽  
Normal Meiosis

Abstract Microtubule-severing protein (MTSP) is critical for the survival of both mitotic and postmitotic cells. However, the study of MTSP during meiosis of mammalian oocytes has not been reported. We found that spastin, a member of the MTSP family, was highly expressed in oocytes and aggregated in spindle microtubules. After knocking down spastin by specific siRNA, the spindle microtubule density of meiotic oocytes decreased significantly. When the oocytes were cultured in vitro, the oocytes lacking spastin showed an obvious maturation disorder. Considering the microtubule-severing activity of spastin, we speculate that spastin on spindles may increase the number of microtubule broken ends by severing the microtubules, therefore playing a nucleating role, promoting spindle assembly and ensuring normal meiosis. In addition, we found the colocalization and interaction of collapsin response mediator protein 5 (CRMP5) and spastin in oocytes. CRMP5 can provide structural support and promote microtubule aggregation, creating transportation routes, and can interact with spastin in the microtubule activity of nerve cells (30). Knocking down CRMP5 may lead to spindle abnormalities and developmental disorders in oocytes. Overexpression of spastin may reverse the abnormal phenotype caused by the deletion of CRMP5. In summary, our data support a model in which the interaction between spastin and CRMP5 promotes the assembly of spindle microtubules in oocytes by controlling microtubule dynamics, therefore ensuring normal meiosis.

The protein interactome of collapsin response mediator protein-2 (CRMP2/DPYSL2) reveals novel partner proteins in brain tissue

2015 ◽  
Vol 9 (9-10) ◽  
pp. 817-831 ◽  
Author(s):  
Daniel Martins-de-Souza ◽  
Juliana S. Cassoli ◽  
Juliana M. Nascimento ◽  
Kenneth Hensley ◽  
Paul C. Guest ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Collapsin Response Mediator Protein ◽  
Protein Interactome ◽  
Mediator Protein ◽  
Partner Proteins
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