scholarly journals Phosphorylation of Collapsin Response Mediator Protein-2 by Rho-kinase

2000 ◽  
Vol 275 (31) ◽  
pp. 23973-23980 ◽  
Author(s):  
Nariko Arimura ◽  
Naoyuki Inagaki ◽  
Kazuyasu Chihara ◽  
Céline Ménager ◽  
Nao Nakamura ◽  
...  
Keyword(s):  
Rho Kinase ◽  
Collapsin Response Mediator Protein ◽  
Mediator Protein

scholarly journals Collapsin Response Mediator Protein Switches RhoA and Rac1 Morphology in N1E-115 Neuroblastoma Cells and Is Regulated by Rho Kinase

2001 ◽  
Vol 276 (46) ◽  
pp. 43482-43486 ◽  
Author(s):  
Christine Hall ◽  
Matthew Brown ◽  
Tom Jacobs ◽  
Giovanna Ferrari ◽  
Nansi Cann ◽  
...  
Keyword(s):  
Neuroblastoma Cells ◽  
Rho Kinase ◽  
Collapsin Response Mediator Protein ◽  
Mediator Protein

scholarly journals Tau-tubulin kinase 1 and amyloid-β peptide induce phosphorylation of collapsin response mediator protein-2 and enhance neurite degeneration in Alzheimer disease mouse models

2019 ◽  
Author(s):  
Seiko Ikezu ◽  
Kaitlin L. Ingraham Dixie ◽  
Lacin Koro ◽  
Takashi Watanabe ◽  
Kozo Kaibuchi ◽  
...  
Keyword(s):  
Rho Kinase ◽  
Amyloid Β ◽  
Dominant Negative ◽  
Perforant Path ◽  
Amyloid Β Peptide ◽  
Dependent Manner ◽  
Collapsin Response Mediator Protein ◽  
Mediator Protein ◽  
Neurite Degeneration

AbstractThe accumulation of phosphorylated tau protein (pTau) in the entorhinal cortex (EC) is the earliest tau pathology in Alzheimer’s disease (AD). Tau tubulin kinase-1 (TTBK1) is a neuron-specific tau kinase and expressed in the EC and hippocampal regions in both human and mouse brains. Here we report that collapsin response mediator protein-2 (CRMP2), a critical mediator of growth cone collapse, is a new downstream target of TTBK1 and is accumulated in the EC region of early stage AD brains. TTBK1 transgenic mice show severe axonal degeneration in the perforant path, which is exacerbated by crossing with Tg2576 mice expressing Swedish familial AD mutant of amyloid precursor protein (APP). TTBK1 mice show accumulation of phosphorylated CRMP2 (pCRMP2), in the EC at 10 months of age, whereas age-matched APP/TTBK1 bigenic mice show pCRMP2 accumulation in both the EC and hippocampal regions. Amyloid-β peptide (Aβ) and TTBK1 suppresses the kinetics of microtubule polymerization and TTBK1 reduces the neurite length of primary cultured neurons in Rho kinase-dependent manner in vitro. Silencing of TTBK1 or expression of dominant-negative Rho kinase demonstrates that Aβ induces CRMP2 phosphorylation at threonine 514 in a TTBK1-dependent manner, and TTBK1 enhances Aβ-induced CRMP2 phosphorylation in Rho kinase-dependent manner in vitro. Furthermore, TTBK1 expression induces pCRMP2 complex formation with pTau in vitro, which is enhanced upon Aβ stimulation in vitro. Finally, pCRMP2 forms a complex with pTau in the EC tissue of TTBK1 mice in vivo, which is exacerbated in both the EC and hippocampal tissues in APP/TTBK1 mice. These results suggest that TTBK1 and Aβ synergistically induce phosphorylation of CRMP2, which may be causative for the neurite degeneration and somal accumulation of pTau in the EC neurons, indicating critical involvement of TTBK1 and pCRMP2 in the early AD pathology.

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

scholarly journals Genetic suppression of collapsin response mediator protein 2 phosphorylation improves outcome in methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson’s model mice

2018 ◽  
Vol 24 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Kentaro Togashi ◽  
Masaya Hasegawa ◽  
Jun Nagai ◽  
Aine Tonouchi ◽  
Daiki Masukawa ◽  
...  
Keyword(s):  
Collapsin Response Mediator Protein ◽  
Mediator Protein ◽  
Genetic Suppression

scholarly journals Loss of CRMP2 O-GlcNAcylation leads to reduced novel object recognition performance in mice

Open Biology ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 190192 ◽  
Author(s):  
Villo Muha ◽  
Ritchie Williamson ◽  
Rachel Hills ◽  
Alison D. McNeilly ◽  
Thomas G. McWilliams ◽  
...  
Keyword(s):  
Nervous System ◽  
Memory Impairment ◽  
Recognition Performance ◽  
Novel Object Recognition ◽  
Small Decrease ◽  
Post Translational Modification ◽  
Site Specific ◽  
Novel Object ◽  
Collapsin Response Mediator Protein ◽  
Mediator Protein

O-GlcNAcylation is an abundant post-translational modification in the nervous system, linked to both neurodevelopmental and neurodegenerative disease. However, the mechanistic links between these phenotypes and site-specific O-GlcNAcylation remain largely unexplored. Here, we show that Ser517 O-GlcNAcylation of the microtubule-binding protein Collapsin Response Mediator Protein-2 (CRMP2) increases with age. By generating and characterizing a Crmp2 S517A knock-in mouse model, we demonstrate that loss of O-GlcNAcylation leads to a small decrease in body weight and mild memory impairment, suggesting that Ser517 O-GlcNAcylation has a small but detectable impact on mouse physiology and cognitive function.

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