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Collapsin response mediator protein

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https://www.readbyqxmd.com/read/28277940/a-single-structurally-conserved-sumoylation-site-in-crmp2-controls-nav1-7-function
#1
Erik Thomas Dustrude, Samantha Perez-Miller, Liberty François-Moutal, Aubin Moutal, May Khanna, Rajesh Khanna
The neuronal collapsin response mediator protein 2 (CRMP2) undergoes several posttranslational modifications that codify its functions. Most recently, CRMP2 SUMOylation (addition of small ubiquitin like modifier (SUMO)) was identified as a key regulatory step within a modification program that codes for CRMP2 interaction with, and trafficking of, voltage-gated sodium channel NaV1.7. In this paper, we illustrate the utility of combining sequence alignment within protein families with structural analysis to identify, from several putative SUMOylation sites, those that are most likely to be biologically relevant...
February 28, 2017: Channels
https://www.readbyqxmd.com/read/28271640/neuroprotective-effect-of-lacosamide-on-hypoxic-ischemic-brain-injury-in-neonatal-rats
#2
Gun Ha Kim, Jung Hye Byeon, Baik Lin Eun
BACKGROUND AND PURPOSE: Lacosamide (LCM) is an antiepileptic drug that enhances the slow inactivation of sodium channels and modulates collapsin response mediator protein-2. LCM was recently demonstrated to exert a neuroprotective effect in a murine model of traumatic brain injury and status epilepticus. Assuming the same underlying excitotoxicity-related brain injury mechanism, we hypothesized that LCM would have a neuroprotective effect in hypoxic-ischemic brain injury. METHODS: We divided rats into three groups at each testing session: pre- or postfed with LCM, fed with normal saline, and sham...
March 6, 2017: Journal of Clinical Neurology
https://www.readbyqxmd.com/read/28254884/a-functional-coupling-between-crmp1-and-nav1-7-for-retrograde-propagation-of-semaphorin3a-signaling
#3
Masayuki Yamane, Naoya Yamashita, Tomonobu Hida, Yoshinori Kamiya, Fumio Nakamura, Pappachan Kolattukudy, Yoshio Goshima
Semaphorin3A (Sema3A) is a secreted type of axon guidance molecules that regulates axon wiring through neuropilin-1 (NRP1) and PlexinAs (PlexAs) receptor complex. Sema3A regulates the dendritic branching through a tetrodotoxin (TTX)-sensitive retrograde axonal transport of PlexAs and Tropomyosin-related kinase A (TrkA) complex. We here demonstrate that Nav1.7, a TTX-sensitive Na(+) channel, by coupling with collapsin response mediator protein 1 (CRMP1), mediates the Sema3A-induced retrograde transport. In mouse dorsal root ganglion (DRG) neurons, Sema3A increased co-localization of PlexA4 and TrkA in the growth cones and axons...
March 2, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28161890/homology-guided-mutational-analysis-reveals-the-functional-requirements-for-antinociceptive-specificity-of-collapsin-response-mediator-protein-2-derived-peptides
#4
Aubin Moutal, Wennan Li, Yue Wang, Weina Ju, Shizhen Luo, Song Cai, Liberty François-Moutal, Samantha Perez-Miller, Jackie Hu, Erik T Dustrude, Todd W Vanderah, Vijay Gokhale, May Khanna, Rajesh Khanna
BACKGROUND AND PURPOSE: N-type voltage-gated calcium (Cav 2.2) channels are critical determinants of increased neuronal excitability and neurotransmission accompanying persistent neuropathic pain. Although Cav 2.2 channel antagonists are recommended as first-line treatment for neuropathic pain, calcium-current blocking gabapentinoids inadequately alleviate chronic pain symptoms and often exhibit numerous side effects. Collapsin response mediator protein 2 (CRMP2) targets Cav 2.2 channels to the sensory neuron membrane and allosterically modulates their function...
February 5, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28122909/prospective-study-of-crmp4-promoter-methylation-in-prostate-biopsies-as-a-predictor-for-lymph-node-metastases
#5
Xin Gao, Liao-Yuan Li, Jörg Rassler, Jun Pang, Ming-Kun Chen, Wei-Peng Liu, Zheng Chen, Shan-Cheng Ren, Fang-Jian Zhou, Ke-Ji Xie, Xing Zhou, Hui-Jun Qian, Xian-Zhong Bai, Jiu-Min Liu, Jiang-Gen Yang, Dan He, Chun-Kui Shao, Zu-Lan Su, Jing Wang, Jian-Guang Qiu, Li Ling
BACKGROUND: For patients with prostate cancer (PCa), the presence of pelvic lymph node metastasis (LNM) is a strong predictor of poor outcome. However, the approaches with promising sensitivity and specificity to detect LNM are still lacking. We investigated the value of collapsin response mediator protein 4 (CRMP4) promoter methylation in biopsies as a predictor for LNM. METHODS: CRMP4 promoter methylation at two previously identified CpG sites was determined in 80 case-matched biopsy samples (the training set) using bisulfite pyrosequencing...
January 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28101231/the-biological-significance-of-methylome-differences-in-human-papilloma-virus-associated-head-and-neck-cancer
#6
Maria J Worsham, Kang Mei Chen, Indrani Datta, Josena K Stephen, Dhananjay Chitale, Alexandra Gothard, George Divine
In recent years, studies have suggested that promoter methylation in human papilloma virus (HPV) positive head and neck squamous cell carcinoma (HNSCC) has a mechanistic role and has the potential to improve patient survival. The present study aimed to replicate key molecular findings from previous analyses of the methylomes of HPV positive and HPV negative HNSCC in an independent cohort, to assess the reliability of differentially methylated markers in HPV-associated tumors. HPV was measured using real-time quantitative PCR and the biological significance of methylation differences was assessed by Ingenuity Pathway Analysis (IPA)...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28044206/collapsin-response-mediator-protein-2-high-resolution-crystal-structure-sheds-light-on-small-molecule-binding-post-translational-modifications-and-conformational-flexibility
#7
Matti Myllykoski, Anne Baumann, Kenneth Hensley, Petri Kursula
Collapsin response mediator protein 2 (CRMP-2) is a neuronal protein involved in axonal pathfinding. Intense research is focusing on its role in various neurological diseases. Despite a wealth of studies, not much is known about the molecular mechanisms of CRMP-2 function in vivo. The detailed structure-function relationships of CRMP-2 have also largely remained unknown, in part due to the fact that the available crystal structures lack the C-terminal tail, which is known to be a target for many post-translational modifications and protein interactions...
April 2017: Amino Acids
https://www.readbyqxmd.com/read/28025999/mir-200a-3p-promotes-the-proliferation-of-human-esophageal-cancer-cells-by-post-transcriptionally-regulating-cytoplasmic-collapsin-response-mediator-protein-1
#8
Yanzi Zang, Yong Tai, Baoluo Wan, Xiaodong Jia
The dysregulation of cytoplasmic collapsin response mediator protein 1 (CRMP1) has been reported in lung cancer, medulloblastoma and esophageal cancer. However, the role of CRMP1 and its regulatory mechanisms in esophageal cancer remain unclear. In this study, we demonstrated that CRMP1 expression was downregulated in esophageal cancer tissues and that there were differences in its expression levels in different esophageal cancer cell lines. We found that CRMP1 overexpression inhibited the proliferation of esophageal cancer cells, whereas the silencing of CRMP1 promoted cell proliferation...
November 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27940916/hierarchical-crmp2-posttranslational-modifications-control-nav1-7-function
#9
Erik T Dustrude, Aubin Moutal, Xiaofang Yang, Yuying Wang, May Khanna, Rajesh Khanna
Voltage-gated sodium channels are crucial determinants of neuronal excitability and signaling. Trafficking of the voltage-gated sodium channel NaV1.7 is dysregulated in neuropathic pain. We identify a trafficking program for NaV1.7 driven by hierarchical interactions with posttranslationally modified versions of the binding partner collapsin response mediator protein 2 (CRMP2). The binding described between CRMP2 and NaV1.7 was enhanced by conjugation of CRMP2 with small ubiquitin-like modifier (SUMO) and further controlled by the phosphorylation status of CRMP2...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27917413/efficacy-of-s-lacosamide-in-preclinical-models-of-cephalic-pain
#10
Aubin Moutal, Nathan Eyde, Edwin Telemi, Ki Duk Park, Jennifer Y Xie, David W Dodick, Frank Porreca, Rajesh Khanna
Migraine is one of the world's most common neurological disorders. Current acute migraine treatments have sub-optimal efficacy and new therapeutic options are needed. Approaches targeting calcitonin gene related peptide (CGRP) signaling are clinically effective but small molecule antagonists have not been advanced due to toxicity. In this study, we explored the axonal growth/specification collapsin response mediator protein 2 (CRMP2) as a novel "druggable" target for inhibiting CGRP release and for potential relevance for treatment of migraine pain...
June 2016: Pain Reports (Baltimore, Md.)
https://www.readbyqxmd.com/read/27864146/microrna-187-regulates-gastric-cancer-progression-by-targeting-the-tumor-suppressor-crmp1
#11
Lian Ren, Fang Li, Maojun Di, Yingfeng Fu, Yuanjian Hui, Gaochun Xiao, Qiang Sun, Yanwei Liu, Dan Ren, Xian Du
Aberrant expression of microRNAs contributes to the initiation and progression of numerous human cancers. The underlying effects and molecular mechanisms of microRNA-187 (miR-187) in gastric cancer (GC) remain unclear. The present study reports that miR-187 was significantly overexpressed in GC tissues compared to that in non-tumor tissues and was associated with malignant clinical factors such as depth of invasion (P = 0.005), tumor size (P = 0.024), lymph node metastasis (P = 0.048), and TNM stage (P = 0...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27845394/calpain-mediated-cleavage-of-collapsin-response-mediator-protein-2-drives-acute-axonal-degeneration
#12
Jian-Nan Zhang, Uwe Michel, Christof Lenz, Caroline C Friedel, Sarah Köster, Zara d'Hedouville, Lars Tönges, Henning Urlaub, Mathias Bähr, Paul Lingor, Jan C Koch
Axonal degeneration is a key initiating event in many neurological diseases. Focal lesions to axons result in a rapid disintegration of the perilesional axon by acute axonal degeneration (AAD) within several hours. However, the underlying molecular mechanisms of AAD are only incompletely understood. Here, we studied AAD in vivo through live-imaging of the rat optic nerve and in vitro in primary rat cortical neurons in microfluidic chambers. We found that calpain is activated early during AAD of the optic nerve and that calpain inhibition completely inhibits axonal fragmentation on the proximal side of the crush while it attenuates AAD on the distal side...
November 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27836492/crmp1-and-crmp4-are-required-for-proper-orientation-of-dendrites-of-cerebral-pyramidal-neurons-in-the-developing-mouse-brain
#13
Ryosuke Takaya, Jun Nagai, Wenfui Piao, Emi Niisato, Takeru Nakabayashi, Yuki Yamazaki, Fumio Nakamura, Naoya Yamashita, Papachan Kolattukudy, Yoshio Goshima, Toshio Ohshima
Neural circuit formation is a critical process in brain development. Axon guidance molecules, their receptors, and intracellular mediators are important to establish neural circuits. Collapsin response mediator proteins (CRMPs) are known intercellular mediators of a number of repulsive guidance molecules. Studies of mutant mice suggest roles of CRMPs in dendrite development. However, molecular mechanisms of CRMP-mediated dendritic development remain to elucidate. In this study, we show abnormal orientation of basal dendrites (extension to deeper side) of layer V pyramidal neurons in the cerebral cortex of CRMP4-/- mice...
January 15, 2017: Brain Research
https://www.readbyqxmd.com/read/27765673/bone-marrow-stromal-cells-promote-neuroplasticity-of-cerebral-ischemic-rats-via-a-phosphorylated-crmp2-mediated-mechanism
#14
Xiang He, Ling Jiang, Qi-Qin Dan, Qiang Lv, Yue Hu, Jia Liu, Shu-Fen Wang, Ting-Hua Wang
Collapsin response mediator protein 2 (CRMP2), an important protein involved in axonal growth and the maintenance of neuronal membrane integrity, has proved to be altered in nervous system diseases. This study was aimed to investigate the role of CRMP2 in bone marrow stromal cells (BMSCs) treating rats with cerebral ischemia. BMSCs were isolated from shaft of the femurs, tibiae, and humeri and were intra-carotid administrated immediately after middle cerebral artery occlusion (MCAO). Modified Neurological Severity Scores (mNSS) was conducted at 3, 7, 14dpo and the electrophysiologic evaluation was evaluated at 14dpo...
October 17, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27759576/paraneoplastic-optic-neuropathy-associated-with-purkinje-cell-antibody-2-in-a-patient-with-small-cell-lung-cancer
#15
Jonathan A Micieli, Edward A Margolin
Paraneoplastic optic neuropathy (PON) is a rare cause of vision loss usually associated with small cell lung cancer. Patients with this condition usually test positive for anti-collapsin response mediating protein-5 (CRMP-5). We describe a case of a 57-year-old woman with bilateral vision loss with the characteristic features of CRMP-5 PON including bilateral optic disc edema and vitreous cells. However, she was negative for anti-CRMP-5 including a negative Western blot on two occasions, but positive for Purkinje Cell Antibody (PCA)-2...
March 2017: Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society
https://www.readbyqxmd.com/read/27698685/targeting-crmp-4-by-lentivirus-mediated-rna-interference-inhibits-sw480-cell-proliferation-and-colorectal-cancer-growth
#16
Si-Le Chen, Shi-Rong Cai, Xin-Hua Zhang, Wen-Feng Li, Er-Tao Zhai, Jian-Jun Peng, Hui Wu, Chuang-Qi Chen, Jin-Ping Ma, Zhao Wang, Yu-Long He
The aim of the present study was to investigate the expression level of collapsin response mediator protein 4 (CRMP-4) in human colorectal cancer (CRC) tissue and to evauluate its impact on SW480 cell proliferation, in addition to tumor growth in a mouse xenograft model. Clinical CRC tissue samples were collected to detect the CRMP-4 protein expression levels using western blot and immunohistochemistry analyses. A specific small interfering RNA sequence targeting the CRMP-4 gene (DPYSL3) was constructed and transfected into an SW480 cell line using a lentivirus vector to obtain a stable cell line with low expression of CRMP-4...
October 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27643908/autoantibody-associated-central-nervous-system-neurologic-disorders
#17
Jenny Linnoila, Sean J Pittock
Autoimmune neurology is a rapidly evolving new subspecialty driven by the discovery of novel neural- (neuronal- or glial-) specific autoantibodies and their target antigens. The neurologic manifestations affecting the central nervous system include encephalitis, dementia, epilepsy, and movement and sleep disorders. Laboratory testing is now available for most of these neural-specific autoantibodies, which serve as diagnostic markers, in some instances directing the physician toward specific cancer types (e...
August 2016: Seminars in Neurology
https://www.readbyqxmd.com/read/27639450/a-novel-mouse-model-for-the-identification-of-thioredoxin-1-protein-interactions
#18
Michelle L Booze, Jason M Hansen, Peter F Vitiello
Thiol switches are important regulators of cellular signaling and are coordinated by several redox enzyme systems including thioredoxins, peroxiredoxins, and glutathione. Thioredoxin-1 (Trx1), in particular, is an important signaling molecule not only in response to redox perturbations, but also in cellular growth, regulation of gene expression, and apoptosis. The active site of this enzyme is a highly conserved C-G-P-C motif and the redox mechanism of Trx1 is rapid which presents a challenge in determining specific substrates...
October 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27609071/increased-phosphorylation-of-collapsin-response-mediator-protein-2-at-thr514-correlates-with-%C3%AE-amyloid-burden-and-synaptic-deficits-in-lewy-body-dementias
#19
Huayang Xing, Yun-An Lim, Joyce R Chong, Jasinda H Lee, Dag Aarsland, Clive G Ballard, Paul T Francis, Christopher P Chen, Mitchell K P Lai
Collapsin response mediator protein-2 (CRMP2) regulates axonal growth cone extension, and increased CRMP2 phosphorylation may lead to axonal degeneration. Axonal and synaptic pathology is an important feature of Lewy body dementias (LBD), but the state of CRMP2 phosphorylation (pCRMP2) as well as its correlations with markers of neurodegeneration have not been studied in these dementias. Hence, we measured CRMP2 phosphorylation at Thr509, Thr514 and Ser522, as well as markers of β-amyloid (Aβ), tau-phosphorylation, α-synuclein and synaptic function in the postmortem neocortex of a longitudinally assessed cohort of LBD patients characterized by low (Parkinson's disease dementia, PDD) and high (dementia with Lewy bodies, DLB) burden of Alzheimer type pathology...
September 8, 2016: Molecular Brain
https://www.readbyqxmd.com/read/27582038/comprehensive-behavioral-study-and-proteomic-analyses-of-crmp2-deficient-mice
#20
Haruko Nakamura, Naoya Yamashita, Ayuko Kimura, Yayoi Kimura, Hisashi Hirano, Hiroko Makihara, Yuko Kawamoto, Aoi Jitsuki-Takahashi, Kumiko Yonezaki, Kenkichi Takase, Tomoyuki Miyazaki, Fumio Nakamura, Fumiaki Tanaka, Yoshio Goshima
Collapsin response mediator protein 2 (CRMP2) plays a key role in axon guidance, dendritic morphogenesis and cell polarization. CRMP2 is implicated in various neurological and psychiatric disorders. However, in vivo functions of CRMP2 remain unknown. We generated CRMP2 gene-deficient (crmp2(-/-) ) mice and examined their behavioral phenotypes. During 24-h home cage monitoring, the activity level during the dark phase of crmp2(-/-) mice was significantly higher than that of wild-type (WT) mice. Moreover, the time during the open arm of an elevated plus maze was longer for crmp2(-/-) mice than for WT mice...
October 2016: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
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