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Collapsin response mediator protein

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https://www.readbyqxmd.com/read/28878401/structural-basis-for-crmp2-induced-axonal-microtubule-formation
#1
Shinsuke Niwa, Fumio Nakamura, Yuri Tomabechi, Mari Aoki, Hideki Shigematsu, Takashi Matsumoto, Atsushi Yamagata, Shuya Fukai, Nobutaka Hirokawa, Yoshio Goshima, Mikako Shirouzu, Ryo Nitta
Microtubule associated protein Collapsin response mediator protein 2 (CRMP2) regulates neuronal polarity in developing neurons through interactions with tubulins or microtubules. However, how CRMP2 promotes axonal formation by affecting microtubule behavior remains unknown. This study aimed to obtain the structural basis for CRMP2-tubulin/microtubule interaction in the course of axonogenesis. The X-ray structural studies indicated that the main interface to the soluble tubulin-dimer is the last helix H19 of CRMP2 that is distinct from the known C-terminal tail-mediated interaction with assembled microtubules...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28864883/transcriptional-regulation-of-crmp5-controls-neurite-outgrowth-through-sox5
#2
Nicolas Naudet, Aubin Moutal, Hong Nhung Vu, Naura Chounlamountri, Chantal Watrin, Sylvie Cavagna, Céline Malleval, Claire Benetollo, Claire Bardel, Marie-Aimée Dronne, Jérôme Honnorat, Claire Meissirel, Roger Besançon
Transcriptional regulation of proteins involved in neuronal polarity is a key process that underlies the ability of neurons to transfer information in the central nervous system. The Collapsin Response Mediator Protein (CRMP) family is best known for its role in neurite outgrowth regulation conducting to neuronal polarity and axonal guidance, including CRMP5 that drives dendrite differentiation. Although CRMP5 is able to control dendritic development, the regulation of its expression remains poorly understood...
September 1, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28837387/crmp2-is-necessary-for-neurofibromatosis-type-1-related-pain
#3
Aubin Moutal, Song Cai, Shizhen Luo, Raphaëlle Voisin, Rajesh Khanna
Neurofibromatosis type 1 (NF1) is one of the most common genetic diseases, affecting roughly 1 in 3000 individuals. As a multisystem disorder, it affects cognitive development, as well as bone, nerve and muscle constitution. Peripheral neuropathy in NF1 constitutes a potentially severe clinical complication and is associated with increased morbidity and mortality. The discovery of effective therapies for Neurofibromatosis type 1 (NF1) pain depends on mechanistic understanding that has been limited, in part, by the relative lack of availability of animal models relevant to NF1 pain...
August 24, 2017: Channels
https://www.readbyqxmd.com/read/28809766/crispr-cas9-editing-of-nf1-gene-identifies-crmp2-as-a-therapeutic-target-in-neurofibromatosis-type-1-nf1-related-pain-that-is-reversed-by-s-lacosamide
#4
Aubin Moutal, Xiaofang Yang, Wennan Li, Kerry B Gilbraith, Shizhen Luo, Song Cai, Liberty François-Moutal, Lindsey A Chew, Seul Ki Yeon, Shreya S Bellampalli, Chaoling Qu, Jennifer Y Xie, Mohab M Ibrahim, May Khanna, Ki Duk Park, Frank Porreca, Rajesh Khanna
Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disease linked to mutations of the Nf1 gene. NF1 patients commonly experience severe pain. Studies on mice with Nf1 haploinsufficiency have been instructive in identifying sensitization of ion channels as a possible cause underlying the heightened pain suffered by NF1 patients. However, behavioral assessments of Nf1+/- mice have led to uncertain conclusions about the potential causal role of Nf1 in pain. We used the clustered regularly interspaced short palindromic repeats/(CRISPR)-associated 9 (CRISPR/Cas9) genome editing system to create and mechanistically characterize a novel rat model of NF1-related pain...
July 3, 2017: Pain
https://www.readbyqxmd.com/read/28767512/dissecting-the-role-of-the-crmp2-neurofibromin-complex-on-pain-behaviors
#5
Aubin Moutal, Yue Wang, Xiaofang Yang, Yingshi Ji, Shizhen Luo, Angie Dorame, Shreya S Bellampalli, Lindsey A Chew, Song Cai, Erik T Dustrude, James E Keener, Michael T Marty, Todd W Vanderah, Rajesh Khanna
Neurofibromatosis type 1 (NF1), a genetic disorder linked to inactivating mutations or homozygous deletion of the Nf1 gene, is characterized by tumorigenesis, cognitive dysfunction, seizures, migraine, and pain. Omic studies on human NF1 tissues identified an increase in expression of collapsin response mediator protein 2 (CRMP2), a cytosolic protein reported to regulate the trafficking and activity of presynaptic N-type voltage-gated calcium (Cav2.2) channels. Since neurofibromin, the protein product of the Nf1 gene, binds to and inhibits CRMP2, the neurofibromin-CRMP2 signaling cascade will likely affect Ca2+ channel activity and regulate nociceptive neurotransmission and in vivo responses to noxious stimulation...
July 31, 2017: Pain
https://www.readbyqxmd.com/read/28726921/molecular-dynamics-simulations-and-in-vitro-analysis-of-the-crmp2-thiol-switch
#6
Daniel Möller, Manuela Gellert, Walter Langel, Christopher Horst Lillig
The collapsin response mediator protein CRMP2 (gene: DPYSL2) is crucial for neuronal development. The homotetrameric CRMP2 complex is regulated via two mechanisms: first by phosphorylation and second by the reduction and oxidation of the Cys504 residues of two adjacent subunits. Here, we have analysed the effects of this redox switch on the protein in vitro combined with force field molecular dynamics (MD). Earlier X-ray data reveal the structure of the rigid body of the molecule but lack the flexible C-terminus with the important sites for phosphorylation and redox regulation...
August 22, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28677754/active-exercise-promotes-achilles-tendon-healing-and-is-accompanied-by-the-upregulation-of-collapsin-response-mediator-protein%C3%A2-2-in-rats
#7
Bayixiati Qianman, Ayidaer Jialihasi, Batiza Asilehan, Aliya Kubai, Rakimbaiev Aibek, Aikeremu Wupuer, Wulanbai Tangkejie, Abudouheilil Maimaitiaili, Nuerai Shawutali, Aynaz Badelhan, Adili Aizezi, Amuding Aisaiding, Jianati Wuerliebieke, Yerzat Bakyt, Elihaer Makemutibieke, Jiasharete Jielile
Collapsin response mediator protein-2 (CRMP-2) is involved in neurite elongation and regeneration; however, its role in wound healing remains to be elucidated. The present study aimed to investigate the effects of active mobilization treatment on Achilles tendon healing and to determine the role of CRMP‑2 in the healing process. Sprague Dawley rats were subjected to Achilles tendon injury, which was verified by hematoxylin and eosin staining and scanning electronic microscopy. Immobilization induced the disruption of collagen fibril arrangement and promoted collagen fibril damage...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28674493/a-systematic-strategy-for-discovering-a-therapeutic-drug-for-alzheimer-s-disease-and-its-target-molecule
#8
Zhiyou Yang, Tomoharu Kuboyama, Chihiro Tohda
Natural medicines are attractive sources of leading compounds that can be used as interventions for neurodegenerative disorders. The complexity of their chemical components and undetermined bio-metabolism have greatly hindered both the use of natural medicines and the identification of their active constituents. Here, we report a systematic strategy for evaluating the bioactive candidates in natural medicines used for Alzheimer's disease (AD). We found that Drynaria Rhizome could enhance memory function and ameliorate AD pathologies in 5XFAD mice...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28663724/activation-of-transient-receptor-potential-vanilloid-4-impairs-the-dendritic-arborization-of-newborn-neurons-in-the-hippocampal-dentate-gyrus-through-the-ampk-and-akt-signaling-pathways
#9
Yujing Tian, Mengwen Qi, Zhouqing Wang, Chunfeng Wu, Zhen Sun, Yingchun Li, Sha Sha, Yimei Du, Lei Chen, Ling Chen
Neurite growth is an important process for the adult hippocampal neurogenesis which is regulated by a specific range of the intracellular free Ca(2+) concentration ([Ca(2+)]i). Transient receptor potential vanilloid 4 (TRPV4) is a calcium-permeable channel and activation of it causes an increase in [Ca(2+)]i. We recently reported that TRPV4 activation promotes the proliferation of stem cells in the adult hippocampal dentate gyrus (DG). The present study aimed to examine the effect of TRPV4 activation on the dendrite morphology of newborn neurons in the adult hippocampal DG...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28660485/crmp2-phosphorylation-drives-glioblastoma-cell-proliferation
#10
Aubin Moutal, Lex Salas Villa, Seul Ki Yeon, Kyle T Householder, Ki Duk Park, Rachael W Sirianni, Rajesh Khanna
Glioblastoma (GBM) is an aggressive primary brain tumor. The rapid growth and the privileged provenance of the tumor within the brain contribute to its aggressivity and poor therapeutic targeting. A poor prognostic factor in glioblastoma is the deletion or mutation of the Nf1 gene. This gene codes for the protein neurofibromin, a tumor suppressor gene that is known to interact with the collapsin response mediator protein 2 (CRMP2). CRMP2 expression and elevated expression of nuclear phosphorylated CRMP2 have recently been implicated in cancer progression...
June 28, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28638064/quantitative-phosphoproteomics-reveals-a-role-for-collapsin-response-mediator-protein-2-in-pdgf-induced-cell-migration
#11
Adil R Sarhan, Justyna Szyroka, Shabana Begum, Michael G Tomlinson, Neil A Hotchin, John K Heath, Debbie L Cunningham
The Platelet Derived Growth Factor (PDGF) family of ligands have well established functions in the induction of cell proliferation and migration during development, tissue homeostasis and interactions between tumours and stroma. However, the mechanisms by which these actions are executed are incompletely understood. Here we report a differential phosphoproteomics study, using a SILAC approach, of PDGF-stimulated mouse embryonic fibroblasts (MEFs). 116 phospho-sites were identified as up-regulated and 45 down-regulated in response to PDGF stimulation...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28616018/collapsin-response-mediator-protein-2-plays-a-major-protective-role-in-acute-axonal-degeneration
#12
REVIEW
Jian-Nan Zhang, Jan C Koch
Axonal degeneration is a key pathological feature in many neurological diseases. It often leads to persistent deficits due to the inability of axons to regenerate in the central nervous system. Therefore therapeutic approaches should optimally both attenuate axonal degeneration and foster axonal regeneration. Compelling evidence suggests that collapsin response mediator protein-2 (CRMP2) might be a molecular target fulfilling these requirements. In this mini-review, we give a compact overview of the known functions of CRMP2 and its molecular interactors in neurite outgrowth and in neurodegenerative conditions...
May 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28524835/collapsin-response-mediator-protein-2-induced-retinal-ischemic-injury-in-a-novel-mice-model-of-ocular-ischemia-syndrome
#13
Yu Wang, Xiao-Lei Wang, Guo-Li Xie, Hong-Yang Li, Yan-Ling Wang
BACKGROUND: Collapsin response mediator protein-2 (CRMP2) has been shown to be involved in ischemia/hypoxia (IH) injury. We determined whether CRMP2 modulates ischemic injury in the retinal of Ocular ischemic syndrome (OIS). This study was to explore the molecular mechanisms underlying OIS in a novel mice model. METHODS: Experiments were performed on adult male C57/BL6 mice that received bilateral internal carotid arteries ligation for 1, 2, or 4 weeks. The mice received injection of calpeptin group before occlusion for 4 weeks or not...
June 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28500272/probing-the-lithium-response-pathway-in-hipscs-implicates-the-phosphoregulatory-set-point-for-a-cytoskeletal-modulator-in-bipolar-pathogenesis
#14
Brian T D Tobe, Andrew M Crain, Alicia M Winquist, Barbara Calabrese, Hiroko Makihara, Wen-Ning Zhao, Jasmin Lalonde, Haruko Nakamura, Glenn Konopaske, Michelle Sidor, Cameron D Pernia, Naoya Yamashita, Moyuka Wada, Yuuka Inoue, Fumio Nakamura, Steven D Sheridan, Ryan W Logan, Michael Brandel, Dongmei Wu, Joshua Hunsberger, Laurel Dorsett, Cordulla Duerr, Ranor C B Basa, Michael J McCarthy, Namrata D Udeshi, Philipp Mertins, Steven A Carr, Guy A Rouleau, Lina Mastrangelo, Jianxue Li, Gustavo J Gutierrez, Laurence M Brill, Nikolaos Venizelos, Guang Chen, Jeffrey S Nye, Husseini Manji, Jeffrey H Price, Colleen A McClung, Hagop S Akiskal, Martin Alda, De-Maw M Chuang, Joseph T Coyle, Yang Liu, Yang D Teng, Toshio Ohshima, Katsuhiko Mikoshiba, Richard L Sidman, Shelley Halpain, Stephen J Haggarty, Yoshio Goshima, Evan Y Snyder
The molecular pathogenesis of bipolar disorder (BPD) is poorly understood. Using human-induced pluripotent stem cells (hiPSCs) to unravel such mechanisms in polygenic diseases is generally challenging. However, hiPSCs from BPD patients responsive to lithium offered unique opportunities to discern lithium's target and hence gain molecular insight into BPD. By profiling the proteomics of BDP-hiPSC-derived neurons, we found that lithium alters the phosphorylation state of collapsin response mediator protein-2 (CRMP2)...
May 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28461116/anti-neuronal-anti-bodies-in-patients-with-early-psychosis
#15
O Mantere, M Saarela, T Kieseppä, T Raij, T Mäntylä, M Lindgren, E Rikandi, W Stoecker, B Teegen, J Suvisaari
It may be challenging to distinguish autoimmune encephalitis associated with anti-neuronal autoantibodies from primary psychiatric disorders. Here, serum was drawn from patients with a first-episode psychosis (n=70) or a clinical high-risk for psychosis (n=6) and controls (n=34). We investigated the serum prevalence of 24 anti-neuronal autoantibodies: IgG antibodies for anti-N-methyl-d-aspartate-type glutamate receptor (anti-NMDAR), glutamate and γ-aminobutyric acid alpha and beta receptors (GABA-a, GABA-b), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA), glycine receptor (GlyR), metabotropic glutamate receptor 1 and 5 (mGluR1, mGluR5), anti-Tr/Delta/notch-like epidermal growth factor-related receptor (DNER), contactin-associated protein-like 2 (CASPR2), myelin oligodendrocyte glycoprotein (MOG), glutamic acid decarboxylase-65 (GAD65), collapsin response mediator protein 5/crossveinless-2 (CV2), aquaporin-4 (AQP4), anti-dipeptidyl-peptidase-like protein-6 (DPPX), type 1 anti-neuronal nuclear antibody (ANNA-1, Hu), Ri, Yo, IgLON5, Ma2, zinc finger protein 4 (ZIC4), Rho GTPase-activating protein 26, amphiphysin, and recoverin, as well as IgA and IgM for dopamine-2-receptor (DRD2)...
April 28, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28445771/cyclin-dependent-kinase-5-collapsin-response-mediator-protein-2-pathway-may-mediate-sevoflurane-induced-dendritic-development-abnormalities-in-rat-cortical-neurons
#16
Yafang Liu, Daowei Lin, Chuiliang Liu, Yifan Zhao, Zhiwen Shen, Kun Zhang, Minghui Cao, Yujuan Li
Sevoflurane has been reported to induce neurotoxicity and cognitive impairment in the developing brains. However, the underlying molecular mechanisms remain poorly understood. Recent studies have demonstrated aberrant cyclin-dependent kinase 5 (CDK5) activity is implicated in inhaled anesthetic-induced neurotoxicity. CDK5/CRMP2 signaling is involved in the cortical and hippocampal dendritic development. The aim of present study is to investigate whether the CDK5/CRMP2 pathway mediates sevoflurane-induced dendritic development abnormalities...
April 24, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28413470/identification-of-genes-associated-with-the-effect-of-inflammation-on-the-neurotransmission-of-vascular-smooth-muscle-cell
#17
Shujie Gan, Shenlong Qiu, Yiwen Feng, Yanping Zhang, Qin Qian, Zhong Wan, Jingdong Tang
Vascular smooth muscle cell (VSMC) accumulation and hypertrophy are common in vascular disorders, and inflammation has a crucial role in the development of these diseases. To investigate the effect of inflammation on the neurotransmission of VSMC, bioinformatic analysis was performed, following next generation sequencing. Genes of lipopolysaccharide (LPS)-treated A7r5 cells and phosphate-buffered saline (PBS)-treated A7r5 cells were sequenced via next generation sequencing, and each assay was repeated three times...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28382925/combined-analysis-of-crmp4-methylation-levels-and-capra-s-score-predicts-metastasis-and-outcomes-in-prostate-cancer-patients
#18
Qun-Xiong Huang, Chu-Tian Xiao, Zheng Chen, Min-Hua Lu, Jun Pang, Jin-Ming Di, Zi-Huan Luo, Xin Gao
The present study analyzed the predictive value of combined analysis of collapsin response mediator protein 4 (CRMP4) methylation levels and the Cancer of the Prostate Risk Assessment (CAPRA-S) Postsurgical score of patients who required adjuvant hormone therapy (AHT) after radical prostatectomy (RP). We retrospectively analyzed 305 patients with prostate cancer (PCa) who received RP and subsequent androgen deprivation therapy (ADT). Two hundred and thirty patients with clinically high-risk PCa underwent immediate ADT, and 75 patients with intermediate risk PCa underwent deferred ADT...
April 4, 2017: Asian Journal of Andrology
https://www.readbyqxmd.com/read/28374915/drp5-is-involved-in-cancer-cell-growth-and-predicts-poor-prognosis-in-human-osteosarcoma
#19
Lin Wang, Weihai Liu, Hengtao Tang, Xianbiao Xie, Changye Zou, Yongqian Wang, Zhenhua Gao, Junqiang Yin
Osteosarcoma is an extremely aggressive primary malignant bone tumor of childhood. Collapsin response mediator proteins (CRMPs), which are highly expressed in the developing nervous system, were recently shown to be associated with cancer development. However, the relationship between DRP5 (CRMP5) and osteosarcoma has not been evaluated. In this study, we investigated the role of DRP5 in the regulation of osteosarcoma growth. DRP5 mRNA and protein levels were significantly upregulated in human osteosarcoma cell lines and associated with increased migration and invasion...
May 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28366719/minocycline-restores-cognitive-relative-altered-proteins-in-young-bile-duct-ligated-rat-prefrontal-cortex
#20
Shih-Wen Li, Yu-Chieh Chen, Jiunn-Ming Sheen, Mei-Hsin Hsu, You-Lin Tain, Kow-Aung Chang, Li-Tung Huang
AIMS: Bile duct ligation (BDL) model is used to study hepatic encephalopathy accompanied by cognitive impairment. We employed the proteomic analysis approach to evaluate cognition-related proteins in the prefrontal cortex of young BDL rats and analyzed the effect of minocycline on these proteins and spatial memory. MAIN METHODS: BDL was induced in young rats at postnatal day 17. Minocycline as a slow-release pellet was implanted into the peritoneum. Morris water maze test and two-dimensional liquid chromatography-tandem mass spectrometry were used to evaluate spatial memory and prefrontal cortex protein expression, respectively...
July 1, 2017: Life Sciences
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