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Haruko Nakamura, Aoi Takahashi-Jitsuki, Hiroko Makihara, Tetsuya Asano, Yayoi Kimura, Jun Nakabayashi, Naoya Yamashita, Yuko Kawamoto, Fumio Nakamura, Toshio Ohshima, Hisashi Hirano, Fumiaki Tanaka, Yoshio Goshima
CRMP2, alternatively designated as DPYSL2, was the first CRMP family member to be identified as an intracellular molecule mediating the signaling of the axon guidance molecule Semaphorin 3A (Sema3A). In Sema3A signaling, cyclin-dependent kinase 5 (Cdk5) primarily phosphorylates CRMP2 at Ser522. Glycogen synthase kinase-3β (GSK-3β) subsequently phosphorylates the residues of Thr509 and Thr514 of CRMP2. Previous studies showed that CRMP2 is involved in pathogenesis of neurological disorders such as Alzheimer's disease...
May 11, 2018: Neurochemistry International
Xin Gao, Yun-Hua Mao, Chutian Xiao, Ke Li, Wei Liu, Liao-Yuan Li, Jun Pang
BACKGROUND: Metastasis is the major cause of cancer-specific death in patients with prostate cancer (PCa). We previously reported that collapsing response mediator protein-4 (CRMP4) is a PCa metastasis-suppressor gene and the hypermethylation in CRMP4 promoter is responsible for the transcription repression in metastatic PCa. However, the underlying mechanisms remain unknown. In this study, we aimed to investigate the role of calpain-2 in CRMP4 promoter hypermethylation and its functional modulation in PCa metastasis...
March 30, 2018: Prostate
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
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
Yiran Zhou, Ruhong Li, Haidong Yu, Ruotian Wang, Zhiqiang Shen
Gastric cancer is one of the most common causes of death worldwide, although its incidence has steadily declined in recent years. There is strong evidence that aberrantly expressed microRNAs (miRNAs) are involved in gastric cancer tumorigenesis. Furthermore, CRMP4 is closely associated with the occurrence and development of gastric cancer, and our predictions suggest that miR-130a, which can promote gastric cancer tumorigenesis, is a potential CRMP4 regulator. In this study, we investigated the expression of CRMP4 and miR-130a in human gastric cancer cell lines by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot (WB) examination and direct interactions between miR-130a and CRMP4 by dual-luciferase reporter assay...
2017: OncoTargets and Therapy
Benyi Li, Changlin Li
Metastasis is the sole cause of cancer death and there is no curable means in clinic. Cellular protein CRMP4 (DPYSL3 gene) was previously defined as a metastasis suppressor in human prostate cancers since its expression is dramatically reduced in lymphatic metastatic diseases and DPYSL3 overexpression in prostate cancer cells significantly suppressed cancer cell migration and invasion. To develop a CRMP4-based antimetastasis therapeutic approach, the small activating RNA (saRNA) technique was utilized to enhance CRMP4 expression in prostate cancer cells...
2017: Advances in Experimental Medicine and Biology
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...
January 2018: Asian Journal of Andrology
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
Basem M Abdallah, Florence Figeac, Kenneth H Larsen, Nicholas Ditzel, Pankaj Keshari, Adiba Isa, Abbas Jafari, Thomas L Andersen, Jean-Marie Delaisse, Yoshio Goshima, Toshio Ohshima, Moustapha Kassem
We identified the neuroprotein collapsing response mediator protein-4 (CRMP4) as a noncanonical osteogenic factor that regulates the differentiation of mouse bone marrow skeletal stem cells (bone marrow stromal stem cells [mBMSCs]) into osteoblastic cells. CRMP4 is the only member of the CRMP1-CRMP5 family to be expressed by mBMSCs and in osteoprogenitors of both adult mouse and human bones. In vitro gain-of-function and loss-of-function of CRMP4 in murine stromal cells revealed its inhibitory effect on osteoblast differentiation...
May 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
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
Haijian Guo, Bing Xia
BACKGROUND: Collapsin response mediator proteins (CRMPs) were originally identified in the nervous system and are involved in neuronal development. Similar to CRMP1, CRMP4 has a shorter transcript encoding a short isoform known as CRMP4a, and a longer transcript encoding a long isoform known as CRMP4b. Previous studies have shown that CRMP4a and CRMP4b exhibit opposing functions in neurite outgrowth. In the present study, we aimed to determine whether CRMP4a and CRMP4b have divergent effects in gastric cancer...
July 30, 2016: BMC Cancer
Caihui Cha, Jifeng Zhang, Zhisheng Ji, Minghui Tan, Sumei Li, Fengming Wu, Keen Chen, Sitang Gong, Guoqing Guo, Hongsheng Lin
CRMP family proteins (CRMPs) are critical for neurite outgrowth and maturation in the developing nervous system. However, the distinct roles of CRMP isoforms remain to be elucidated, especially in dendritic development. Here, we show that CRMP4 is sufficient and necessary for dendritic growth and maturation in cultured hippocampal neurons. Overexpression of CRMP4 promotes and genetic knockdown of CRMP4 inhibits the amount of dendritic tips, total dendritic length, spine density, and the frequency but not amplitude of miniature excitatory synaptic current...
June 2016: Brain Research Bulletin
Sho Sato, Fumio Nakamura, Yukihiko Hiroshima, Yoji Nagashima, Ikuma Kato, Naoya Yamashita, Yoshio Goshima, Itaru Endo
BACKGROUND: Chronic pancreatitis is a significant risk factor for pancreatic cancer. Previously, we demonstrated that the pancreatic cancer cells show enhanced expression of collapsin response mediator protein 4 (CRMP4) that strongly correlates with severe venous invasion, liver metastasis, and poor prognosis. However, involvement of CRMP4 in acute or chronic pancreatitis remains unknown. METHODS: Acute and chronic pancreatitis mice models were developed by periodic injection of caerulein...
July 2016: Journal of Hepato-biliary-pancreatic Sciences
Changlin Li, Wencong Jiang, Qingting Hu, Long-Cheng Li, Liang Dong, Ruibao Chen, Yinghong Zhang, Yuzhe Tang, J Brantley Thrasher, Chang-Bai Liu, Benyi Li
To explore a novel strategy in suppressing tumor metastasis, we took the advantage of a recent RNA activation (RNAa) theory and used small double-strand RNA molecules, termed as small activating RNAs (saRNA) that are complimentary to target gene promoter, to enhance transcription of metastasis suppressor gene. The target gene in this study is Dihydro-pyrimidinase-like 3 (DPYSL3, protein name CRMP4), which was identified as a metastatic suppressor in prostate cancers. There are two transcriptional variants of DPYSL3 gene in human genome, of which the variant 2 is the dominant transcript (DPYSL3v2, CRMP4a) but is also significantly down-regulated in primary prostate cancers...
April 19, 2016: Oncotarget
Jun Nagai, Ryosuke Takaya, Wenhui Piao, Yoshio Goshima, Toshio Ohshima
The capacity for regeneration in the injured adult mammalian central nervous system (CNS) is largely limited by potent inhibitory barriers. Chondroitin sulfate proteoglycans (CSPGs) are major inhibitors of axonal regeneration/sprouting and accumulate at lesion sites after CNS trauma. Despite extensive research during the two decades since their discovery, the molecular mechanisms remain elusive, including intracellular phosphorylation events. Collapsin response mediator protein 4 (CRMP4) is known to directly regulate cytoskeletal dynamics and neurite extension, while phosphorylated CRMP4 loses its binding affinity for cytoskeletal proteins...
July 2016: Molecular and Cellular Neurosciences
Aine Tonouchi, Jun Nagai, Kentaro Togashi, Yoshio Goshima, Toshio Ohshima
Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by the selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Several lines of evidence suggest that neurodegeneration in PD is accelerated by a vicious cycle in which apoptosis in dopaminergic neurons triggers the activation of microglia and harmful inflammatory processes that further amplify neuronal death. Recently, we demonstrated that the deletion of collapsin response mediator protein 4 (CRMP4) suppresses inflammatory responses and cell death in a mouse model of spinal cord injury, leading to improved functional recovery...
June 2016: Journal of Neurochemistry
Sile Chen, Xinhua Zhang, Jianjun Peng, Ertao Zhai, Yulong He, Hui Wu, Chuangqi Chen, Jinping Ma, Zhao Wang, Shirong Cai
This study aimed to investigate the precise role of CRMP4 in gastric tumor growth and patient survival. The mRNA and protein expression levels of CRMP4, VEGF and VEGFR2 were validated by qRT-PCR and immunohistochemistry. We investigated the effects on tumor growth of overexpression and knockdown of CRMP4 both in vitro and in vivo by constructing stable gastric cell lines using lentiviral-mediated transduction and shRNA interference-mediated knockdown of CRMP4 expression. We further validated the role of the ERK/AKT signaling pathways in VEGF and CRMP4 expression using ERK and PI3K inhibitors...
March 29, 2016: Oncotarget
Atsuhiro Tsutiya, Hikaru Watanabe, Yui Nakano, Masugi Nishihara, Yoshio Goshima, Ritsuko Ohtani-Kaneko
Collapsin response mediator protein 4 (CRMP4), a member of the CRMP family, is involved in the pathogenesis of neurodevelopmental disorders such as schizophrenia and autism. Here, we first compared layer thickness of the olfactory bulb between wild-type (WT) and CRMP4-knockout (KO) mice. The mitral cell layer (MCL) was significantly thinner, whereas the external plexiform layer (EPL) was significantly thicker in CRMP4-KO mice at postnatal day 0 (PD0) compared with WTs. However, differences in layer thickness disappeared by PD14...
May 2016: Journal of Anatomy
Atsuhiro Tsutiya, Masugi Nishihara, Yoshio Goshima, Ritsuko Ohtani-Kaneko
Members of the collapsin response mediator protein (CRMP) family are reported to be involved in the pathogenesis of various neuronal disorders, including schizophrenia and autism. One of them, CRMP4, is reported to participate in aspects of neuronal development, such as axonal guidance and dendritic development. However, no physiological or behavioral phenotypes in Crmp4 knockout (Crmp4-KO) mice have been identified, making it difficult to elucidate the in vivo roles of CRMP4. Focusing on the olfaction process because of the previous study showing strong expression of Crmp4 mRNA in the olfactory bulb (OB) during the early postnatal period, it was aimed to test the hypothesis that Crmp4-KO pups would exhibit abnormal olfaction...
September 2015: European Journal of Neuroscience
Minghui Tan, Caihui Cha, Yongheng Ye, Jifeng Zhang, Sumei Li, Fengming Wu, Sitang Gong, Guoqing Guo
Cytoskeleton dynamics are critical phenomena that underpin many fundamental cellular processes. Collapsin response mediator proteins (CRMPs) are highly expressed in the developing nervous system, mediating growth cone guidance, neuronal polarity, and axonal elongation. However, whether and how CRMPs associate with microtubules and actin coordinated cytoskeletal dynamics remain unknown. In this study, we demonstrated that CRMP2 and CRMP4 interacted with tubulin and actin in vitro and colocalized with the cytoskeleton in the transition-zone in developing growth cones...
2015: Neural Plasticity
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