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Collapsin response mediator protein

Takuya Sumi, Tsuyoshi Imasaki, Mari Aoki, Naoki Sakai, Eriko Nitta, Mikako Shirouzu, Ryo Nitta
Collapsin response mediator protein 2 (CRMP2) regulates neuronal polarity by controlling microtubule dynamics. CRMP2 activity is regulated by semaphorin-induced phosphorylation at the C-terminal tail domain. Unphosphorylated CRMP2 induces effective axonal microtubule formation to give the axonal characteristics to a neurite, whereas phosphorylated CRMP2 leads to the apparently opposite effect, growth cone collapse. We have recently characterized the structural detail of CRMP2-induced axonal microtubule formation (Niwa et al...
2018: Cell Structure and Function
Yafang Liu, Chuiliang Liu, Minting Zeng, Xue Han, Kun Zhang, Yanni Fu, Jue Li, Yujuan Li
Prolonged exposure to volatile anesthetics causes neurodegeneration in developing animal brains. However, their underlying mechanisms of action remain unclear. The current study investigated the expression of proteins associated with the mitogen-activated protein kinases (MAPK) and protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β)/collapsin response mediator protein 2 (CRMP-2) signaling pathways in the cortices of neonatal mice following exposure to sevoflurane. Seven-day-old (P7) neonatal C57BL/6 mice were randomly divided into 2 groups and either exposed to 2...
February 2018: Experimental and Therapeutic Medicine
Masanori Nakajima, Ayumi Uchibori, Yuki Ogawa, Tai Miyazaki, Yaeko Ichikawa, Kimihiko Kaneko, Toshiyuki Takahashi, Ichiro Nakashima, Hirokazu Shiraishi, Masakatsu Motomura, Atsuro Chiba
A 61-year-old woman who had smoked for 40 years developed subacute dizziness, ataxic gait, opsoclonus, and right visual impairment. She had right optic disc swelling and optic nerve gadolinium enhancement on magnetic resonance imaging. She had small-cell lung cancer (SCLC), with CV2/collapsin response mediator protein (CRMP) 5 and HuD antibodies in her serum and cerebrospinal fluid. She was diagnosed with paraneoplastic optic neuropathy (PON) accompanied by paraneoplastic opsoclonus-ataxia syndrome. Her symptoms improved after removing the SCLC...
January 11, 2018: Internal Medicine
Zheng Chen, Qiong Liang, Jue Wang, Qun-Xiong Huang, Jian-Ning Chen, Zi-Jin Weng, Chun-Kui Shao, Xin Gao, Jun Pang
Background: Primary malignant lymphoma of the prostate (PMLP) is prone to occur in the elderly, and it has no significant correlation with lactate dehydrogenase (LDH) and prostate specific antigen (PSA). Clinical symptoms and imaging data of PMLP remain unspecific, and its prognosis is poor. A previous result showed that collapsin response mediator protein 4 (CRMP4) promotor methylation can be used as a predictor for lymph node metastases in prostate biopsies. However, the relationship between CRMP4 promotor methylation and PMLP has not been studied...
2018: Cancer Cell International
Divyanshu Dubey, Vanda A Lennon, Avi Gadoth, Sean J Pittock, Eoin P Flanagan, John E Schmeling, Andrew McKeon, Christopher J Klein
OBJECTIVE: To establish the phenotype and clinical outcomes of collapsin response-mediator protein-5 (CRMP5) autoimmune neuropathy in comparison with anti-neuronal nuclear antibody type 1 (ANNA1)-immunoglobulin G (IgG) neuropathy. METHODS: Patients with CRMP5-IgG and/or ANNA1-IgGs were identified in our service-line testing, and medical records were reviewed. RESULTS: One hundred five patients with CRMP5-IgG neuropathy (88% smokers; 69% having cancer, most commonly small cell lung cancer [75%]) were identified and compared to 51 patients with ANNA1-IgG neuropathy, 27 with coexisting CRMP5-IgG...
January 9, 2018: Neurology
Hye Yeon Nam, Eun Jung Na, Eunyoung Lee, Youngjoo Kwon, Hwa-Jung Kim
Oleamide was first known as a sleep-inducing fatty acid amide, and later shown to have wide range of neuropharmacological effects upon different neurochemical systems. However, the effects of oleamide on brain damage have scarcely been studied, and the molecular mechanisms and sites of its action remain elusive. Kainic acid (KA) has been used to produce an epileptic animal model that mimics human temporal lobe epilepsy and to induce calpain-activated excitotoxicity, which occurs in numerous neurodegenerative disorders...
2017: Frontiers in Pharmacology
Atsuhiro Tsutiya, Yui Nakano, Emily Hansen-Kiss, Benjamin Kelly, Masugi Nishihara, Yoshio Goshima, Don Corsmeier, Peter White, Gail E Herman, Ritsuko Ohtani-Kaneko
Autism spectrum disorders (ASD) are more common among boys than girls. The mechanisms responsible for ASD symptoms and their sex differences remain mostly unclear. We previously identified collapsin response mediator protein 4 (CRMP4) as a protein exhibiting sex-different expression during sexual differentiation of the hypothalamic sexually dimorphic nucleus. This study investigated the relationship between the sex-different development of autistic features and CRMP4 deficiency. Whole-exome sequencing detected a de novo variant (S541Y) of CRMP4 in a male ASD patient...
December 1, 2017: Scientific Reports
F Liu, S Laguesse, R Legastelois, N Morisot, S Ben Hamida, D Ron
This corrects the article DOI: 10.1038/mp.2016.12.
November 14, 2017: Molecular Psychiatry
Lihong Nan, Lan Yang, Yanfang Zheng, Yibo He, Qingqing Xie, Zheming Chen, Huang Li, Mei Huang
Gualou Guizhi decoction (GLGZD) is effective for the clinical treatment of limb spasms caused by ischemic stroke, but its underlying mechanism is unclear. Propidium iodide (PI) fluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), immunohistochemistry, western blot, and real-time qPCR were used to observe the axonal regeneration and neuroprotective effects of GLGZD aqueous extract on organotypic cortical slices exposed to oxygen-glucose deprivation (OGD) and further elucidate the potential mechanisms...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
Serena Quarta, Maria Camprubí-Robles, Rüdiger Schweigreiter, Dusan Matusica, Rainer V Haberberger, Richard L Proia, Christine E Bandtlow, Antonio Ferrer-Montiel, Michaela Kress
The bioactive lipid sphingosine-1-phosphate (S1P) is an important regulator in the nervous system. Here, we explored the role of S1P and its receptors in vitro and in preclinical models of peripheral nerve regeneration. Adult sensory neurons and motor neuron-like cells were exposed to S1P in an in vitro assay, and virtually all neurons responded with a rapid retraction of neurites and growth cone collapse which were associated with RhoA and ROCK activation. The S1P1 receptor agonist SEW2871 neither activated RhoA or neurite retraction, nor was S1P-induced neurite retraction mitigated in S1P1-deficient neurons...
2017: Frontiers in Molecular Neuroscience
Eun J Na, Hye Yeon Nam, Jiyoung Park, Myung Ah Chung, Hyun Ae Woo, Hwa-Jung Kim
Collapsin response mediator protein (CRMP)-2 and the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway are associated with common physiological functions such as neuronal polarity, axonal outgrowth and synaptic strength, as well as various brain disorders including epilepsy. But, their regulatory and functional links are unclear. Alterations in CRMP-2 expression that lead to its functional changes are implicated in brain disorders such as epilepsy. Here, we investigate whether changes in CRMP-2 expression, possibly regulated by mTOR-related signaling, correlates with neuronal growth and viability...
2017: Frontiers in Molecular Neuroscience
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
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
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
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. Patients with NF1 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 patients with NF1. 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...
December 2017: Pain
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 a 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 the 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. Because neurofibromin, the protein product of the Nf1 gene, binds to and inhibits CRMP2, the neurofibromin-CRMP2 signaling cascade will likely affect Ca channel activity and regulate nociceptive neurotransmission and in vivo responses to noxious stimulation...
November 2017: Pain
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
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
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
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
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