Molecular cloning and expression of human neurochondrin-1 and -2

Mochizuki, Reiko; Ishizuka, Yasuyuki; Yanai, Kazuyuki; Koga, Yoshihiko; Fukamizu, Akiyoshi

doi:10.1016/s0167-4781(99)00120-7

Cited by 13 publications

(12 citation statements)

References 12 publications

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“…In this study, immunostaining demonstrated the significant tissue or age‐specific expression for a set of novel NP markers, neuronal‐related proteins (Basp1, Ncdn, Nrp1), transcriptional factor (Brachyury T), and CD proteins (CD24, CD54, CD155, CD166, and CD221) between juvenile and adult IVD tissues. Brain abundant membrane attached signal protein1 (Basp1) is a novel myristoylated calmodulin‐binding protein found predominantly in neurons and the spinal cord, which is involved in neurite outgrowth and synaptic plasticity; Neurochondrin (Ncdn) is a cytoplasmic leucine‐rich protein that participates in neurite outgrowth and chondrocyte differentiation; Neuropillin‐1 (Nrp‐1) is a neuronal cell transmembrane glycoprotein that mediates neuronal guidance and angiogenesis . These three neuronal‐associated proteins were found highly expressed in human juvenile NP, not in aged NP or AF tissue.…”

Section: Discussionmentioning

confidence: 99%

Identifying molecular phenotype of nucleus pulposus cells in human intervertebral disc with aging and degeneration

Tang

Jing

Richardson

et al. 2016

Journal Orthopaedic Research

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Previous study claimed that disc degeneration may be preceded by structure and matrix changes in the intervertebral disc (IVD) which coincide with the loss of distinct notochordally-derived nucleus pulposus (NP) cells. However the fate of notochordal cells and their molecular phenotype change during aging and degeneration in human are still unknown. In this study, a set of novel molecular phenotype markers of notochordal NP cells during aging and degeneration in human IVD tissue were revealed with immunostaining and flow cytometry. Furthermore, the potential of phenotype juvenilization and matrix regeneration of IVD cells in a laminin-rich pseudo-3D culture system were evaluated at day 28 by immunostaining, Safranin O and type II collagen staining. Immunostaining and flow cytometry demonstrated that transcriptional factor Brachyury T, neuronal-related proteins (brain abundant membrane attached signal protein 1, Basp1; Neurochondrin, Ncdn; Neuropilin, Nrp-1), CD24 and CD221 were expressed only in juvenile human NP tissue, which suggested that these proteins may be served as the notochordal NP cell markers. However, the increased expression of CD54 and CD166 with aging indicated that they might be referenced as the potential biomarker for disc degeneration. In addition, 3D culture maintained most of markers in juvenile NP, and rescued the expression of Basp1, Ncdn and Nrp 1 that disappeared in adult NP native tissue. These findings provided new insight into molecular profile that may be used to characterize the existence of a unique notochordal NP cells during aging and degeneration in human IVD cells, which will facilitate cell-based therapy for IVD regeneration.

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Section: Discussionmentioning

confidence: 99%

Identifying molecular phenotype of nucleus pulposus cells in human intervertebral disc with aging and degeneration

Tang

Jing

Richardson

et al. 2016

Journal Orthopaedic Research

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“…Neurochondrin (Ncdn), also named norbin in the rat, was first identified in mouse brain [46]. It is a cytoplasmic leucine-rich protein involved in neurite outgrowth and chondrocyte differentiation [47], [48]. Similar to Basp1, Ncdn strongly expressed in rat NP of all age groups (1, 12 and 21 m) at the gene and protein levels, yet its protein expression was not detected in rat AF of any age.…”

Section: Discussionmentioning

confidence: 99%

Changes in the Molecular Phenotype of Nucleus Pulposus Cells with Intervertebral Disc Aging

2012

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Intervertebral disc (IVD) disorder and age-related degeneration are believed to contribute to low back pain. Cell-based therapies represent a promising strategy to treat disc degeneration; however, the cellular and molecular characteristics of disc cells during IVD maturation and aging still remain poorly defined. This study investigated novel molecular markers and their age-related changes in the rat IVD. Affymetrix cDNA microarray analysis was conducted to identify a new set of genes characterizing immature nucleus pulposus (NP) cells. Among these markers, select neuronal-related proteins (Basp1, Ncdn and Nrp-1), transcriptional factor (Brachyury T), and cell surface receptors (CD24, CD90, CD155 and CD221) were confirmed by real-time PCR and immunohistochemical (IHC) staining for differential expression between IVD tissue regions and among various ages (1, 12 and 21 months). NP cells generally possessed higher levels of mRNA or protein expression for all aforementioned markers, with the exception of CD90 in anulus fibrosus (AF) cells. In addition, CD protein (CD24 and CD90) and Brachyury (T) expression in immature disc cells were also confirmed via flow cytometry. Similar to IHC staining, results revealed a higher percentage of immature NP cells expressing CD24 and Brachyury, while higher percentage of immature AF cells was stained positively for CD90. Altogether, this study identifies that tissue-specific gene expression and age-related differential expression of the above markers do exist in immature and aged disc cells. These age-related phenotype changes provide a new insight for a molecular profile that may be used to characterize NP cells for developing cell-based regenerative therapy for IVD regeneration.

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“…The cytoplasmic protein Norbin (neurochondrin) is reported to increase mGluR5 cell surface localization and positively regulate mGluR5 signaling in in vitro systems [38]. Norbin is also critically involved in neurite outgrowth, and thus neuronal plasticity and cognitive functioning [22,30]. Cortical Norbin knock-out mice have reduced mGluR5 cell surface expression and function, and display strong schizophrenia-like behaviors [38].…”

Section: Introductionmentioning

confidence: 99%

Alterations of mGluR5 and its endogenous regulators Norbin, Tamalin and Preso1 in schizophrenia: towards a model of mGluR5 dysregulation

et al. 2015

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. (2015). Alterations of mGluR5 and its endogenous regulators Norbin, Tamalin and Preso1 in schizophrenia: towards a model of mGluR5 dysregulation. Acta Neuropathologica, 130 (1), 119-129. Alterations of mGluR5 and its endogenous regulators Norbin, Tamalin and Preso1 in schizophrenia: towards a model of mGluR5 dysregulation AbstractKnockout of genes encoding metabotropic glutamate receptor 5 (mGluR5) or its endogenous regulators, such as Norbin, induce a schizophrenia-like phenotype in rodents, suggesting dysregulation of mGluR5 in schizophrenia. Human genetic and pharmacological animal studies support this hypothesis, but no studies have explored mGluR5 dysfunction at the molecular level in the postmortem schizophrenia brain. We assessed mGluR5 mRNA and protein levels in the dorsolateral prefrontal cortex (DLPFC) using a large cohort of schizophrenia and control subjects (n = 37/group), and additionally measured protein levels of recently discovered mGluR5 endogenous regulators, Norbin (neurochondrin), Tamalin (GRASP-1), and Preso1 (FRMPD4), which regulate mGluR5 localization, internalization and signaling. While mGluR5 mRNA expression was unchanged, mGluR5 protein levels were significantly higher in schizophrenia subjects compared to controls (total: +22 %; dimer: +54 %; p < 0.001). Conversely, mGluR5 regulatory proteins were expressed at lower levels in schizophrenia subjects compared to controls (Norbin −37 %, p < 0.001; Tamalin −30 %, p = 0.084; Preso1 −29 %, p = 0.001). mGluR5 protein was significantly associated with mGluR5 mRNA and mGluR5 endogenous regulators in control subjects, but these associations were lost in schizophrenia subjects. Lastly, there were no associations between protein measures and lifetime antipsychotic history in schizophrenia subjects. To confirm no antipsychotic influence, all proteins were measured in the prefrontal cortex of rats exposed to haloperidol or olanzapine; there were no effects of antipsychotic drug treatment on mGluR5, Norbin, Tamalin or Preso1. The results from our study provide compelling evidence that mGluR5 regulation is altered in schizophrenia, likely contributing to the altered glutamatergic signaling that is associated with the disorder. AbstractKnockout of genes encoding metabotropic glutamate receptor 5 (mGluR5) or its endogenous regulators, such as Norbin, induce a schizophrenia-like phenotype in rodents, suggesting dysregulation of mGluR5 in schizophrenia. Human genetic and pharmacological animal studies support this hypothesis, but no studies have explored mGluR5 dysfunction at the molecular level in the postmortem schizophrenia brain. We assessed mGluR5 mRNA and protein levels in the dorsolateral prefrontal cortex (DLPFC) using a large cohort of schizophrenia and control subjects (n=37/group), and additionally measured protein levels of recently discovered mGluR5 endogenous regulators, Norbin (neurochondrin), Tamalin (GRASP-1), and Preso1 (FRMPD4), which regulate mGluR5 localization, internalization and signaling. Whilst mGluR5 mRNA expression was unc...

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Molecular cloning and expression of human neurochondrin-1 and -2

Cited by 13 publications

References 12 publications

Identifying molecular phenotype of nucleus pulposus cells in human intervertebral disc with aging and degeneration

Identifying molecular phenotype of nucleus pulposus cells in human intervertebral disc with aging and degeneration

Changes in the Molecular Phenotype of Nucleus Pulposus Cells with Intervertebral Disc Aging

Alterations of mGluR5 and its endogenous regulators Norbin, Tamalin and Preso1 in schizophrenia: towards a model of mGluR5 dysregulation

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