The Selective RNA-binding Protein Quaking I (QKI) Is Necessary and Sufficient for Promoting Oligodendroglia Differentiation

Chen, Yuntao; Tian, Dan; Ku, Li; Osterhout, Donna J.; Feng, Yue

doi:10.1074/jbc.m702045200

Cited by 55 publications

(59 citation statements)

References 44 publications

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“…2 E and F). Furthermore, the selective RNA-binding protein QKI that performs critical functions in promoting OL differentiation and myelination (20) was also significantly reduced in PIKE −/− mice ( Fig. 2 E and F), consistent with the previous report that QKI is a target of mTOR during OPC differentiation (21).…”

Section: Pike-l Is Required For Maintaining Akt/mtor Signaling Duringsupporting

confidence: 79%

PIKEis essential for oligodendroglia development and CNS myelination

Chan¹,

Liu²,

Zhao

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Oligodendrocyte (OL) differentiation and myelin development are complex events regulated by numerous signal transduction factors. Here, we report that phosphoinositide-3 kinase enhancer L (PIKE-L) is required for OL development and myelination. PIKE-L expression is up-regulated when oligodendrocyte progenitor cells commit to differentiation. Conversely, depleting phosphoinositide-3 kinase enhancer (PIKE) expression by shRNA prevents oligodendrocyte progenitor cell differentiation. In both conventional PIKE knockout (PIKE −/− ) and OL-specific PIKE knockout mice, the number of OLs is reduced in the corpus callosum. PIKE −/− OLs also display defects when forming myelin sheath on neuronal axons during neonatal development, which is partially rescued when PTEN is ablated. In addition, Akt/mTOR signaling is impaired in OL-enriched tissues of the PIKE −/− mutant, leading to reduced expression of critical proteins for myelin development and hypomyelination. Moreover, myelin repair of lysolecithin-induced lesions is delayed in PIKE −/− brain. Thus, PIKE plays pivotal roles to advance OL development and myelinogenesis through Akt/mTOR activation.

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Section: Pike-l Is Required For Maintaining Akt/mtor Signaling Duringsupporting

confidence: 79%

PIKEis essential for oligodendroglia development and CNS myelination

Chan¹,

Liu²,

Zhao

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Using an autosomal recessive mutant (qkv) model, the dysfunction of the mouse QKI gene has been well described as related to body tremor and the severe demyelination of the central nervous system [25]. To date, an increasing number of studies have confirmed that the human QKI gene in the brain plays a fundamental role in myelination and ODC differentiation [26,27]. Abnormal QKI expression may be critical in influencing other myelin-associated gene expression abnormalities in psychiatric disorders, such as schizophrenia and MDD.…”

Section: Discussionmentioning

confidence: 99%

Influence of Childhood Physical Neglect on Depression: Potential Moderation by a Polymorphism in the QKI Gene

Geng¹,

Shi²

2016

J Depress Anxiety

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of genetic and environmental factors (e.g., stress) could initially lead to glial cell pathology and consequently contribute to neuronal pathology later in life, as depressive illnesses progresses [13].For these reasons, the present study sought to (i) examine the potential impact of CPN on general functioning, adult depressive symptoms and antidepressant treatment response, and (ii) test whether genetic polymorphisms related to ODC and myelin function interact with CPN to affect adult depressive symptoms and antidepressant response. Methods Study design and subjectsSubjects were Chinese Han individuals aged between 18 to 60 years, with a diagnosis of new or recently relapsed major depression disorder (MDD). The baseline scores on the 17-item Hamilton Depression Rating Scale (HAMD-17) were>17. Exclusion criteria used for this study have been previously reported [14]. All of the subjects were informed of the potential risks and benefits of the study and gave their informed consent prior to their participation in the study. AbstractObjective: Childhood physical neglect (CPN) is a common but often overlooked form of abuse that may contribute to depression. We aimed at examining the potential impact of CPN and its interactions with genes related to oligodendrocytes (ODCs) and myelin function on adult depressive symptoms and antidepressant treatment response.Methods: A group of 209 Chinese Han patients with major depressive disorder (MDD) completed the Hamilton Depression Scale-17 (HAMD-17) at baseline and after 8 weeks antidepressant treatment. The Childhood Trauma Questionnaire was used to evaluate the occurrence of childhood physical neglect. Twelve single nucleotide polymorphisms (SNPs) in functional regions were successfully genotyped in seven genes associated with ODCs and myelin function. Results:Childhood physical neglect is related to education and social support, especially the subjective social support of those who experience CPN. The GG genotype of the 3'UTR functional polymorphism rs715020 in the QKI gene showed significant association with diminished effects of childhood physical neglect on adult depressive symptoms(P=.003) even after the Bonferroni correction. No significant interactions between candidate genes and CPN on antidepressant response were observed. Conclusion:These results indicate that CPN are potentially associated with ODCs and myelin-related gene QKI, and may influence adult depressive symptoms in major depression disorder (MDD) patients. This finding needs to be further replicated in a larger sample.

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“…The identification of MS-CSF reactivity to quaking protein is potentially an important finding, given that the 37 kDa isoform has been shown to be essential for the development of oligodendrocyte progenitor cells by regulating their gene expression toward a promyelinating phenotype (77). Similarly, HSP-70 is required for the optimal expression of MBP (78), with HSP-70 also found to be associated with MBP in MS lesions, in an ATP-dependent fashion (79).…”

Section: Role Of Stress Proteins and Oligodendrocyte And Myelin Protementioning

confidence: 99%

A Novel Unbiased Proteomic Approach to Detect the Reactivity of Cerebrospinal Fluid in Neurological Diseases

Menon

Steer

Short

et al. 2011

Molecular & Cellular Proteomics

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Neurodegenerative diseases, such as multiple sclerosis represent global health issues. Accordingly, there is an urgent need to understand the pathogenesis of this and other central nervous system disorders, so that more effective therapeutics can be developed. Cerebrospinal fluid is a potential source of important reporter molecules released from various cell types as a result of central nervous system pathology. Here, we report the development of an unbiased approach for the detection of reactive cerebrospinal fluid molecules and target brain proteins from patients with multiple sclerosis. To help identify molecules that may serve as clinical biomarkers for multiple sclerosis, we have biotinylated proteins present in the cerebrospinal fluid and tested their reactivity against brain homogenate as well as myelin and myelin-axolemmal complexes. Proteins were separated by two-dimensional gel electrophoresis, blotted onto membranes and probed separately with biotinylated unprocessed cerebrospinal fluid samples. Protein spots that reacted to two or more multiple sclerosis-cerebrospinal fluids were further analyzed by matrix assisted laser desorption ionization-time-of-flight time-of-flight mass spectrometry. In addition to previously reported proteins found in multiple sclerosis cerebrospinal fluid, such as ␣␤ crystallin, enolase, and 14 -3-3-protein, we have identified several additional molecules involved in mitochondrial and energy metabolism, myelin gene expression and/or cytoskeletal organization. These include aspartate aminotransferase, cyclophilin-A, quaking protein, collapsin response mediator protein-2, ubiquitin carboxy-terminal hydrolase L1, and cofilin. To further validate these findings, the cellular expression pattern of collapsin response mediator protein-2 and ubiquitin carboxy-terminal hydrolase L1 were investigated in human chronic-active MS lesions by immunohistochemistry. The observation that in multiple sclerosis lesions phosphorylated collapsin response mediator protein-2 was increased, whereas Ubiquitin carboxy-terminal hydrolase L1 was down-regulated, not only highlights the importance of these molecules in the pathology of this disease, but also illustrates the use of our approach in attempting to decipher the complex pathological processes leading to multiple sclerosis and other neurodegenerative diseases.

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The Selective RNA-binding Protein Quaking I (QKI) Is Necessary and Sufficient for Promoting Oligodendroglia Differentiation

Cited by 55 publications

References 44 publications

PIKEis essential for oligodendroglia development and CNS myelination

PIKEis essential for oligodendroglia development and CNS myelination

Influence of Childhood Physical Neglect on Depression: Potential Moderation by a Polymorphism in the QKI Gene

A Novel Unbiased Proteomic Approach to Detect the Reactivity of Cerebrospinal Fluid in Neurological Diseases

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