RGD Reference Report - CLC-2 is a positive modulator of oligodendrocyte precursor cell differentiation and myelination. - Rat Genome Database

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CLC-2 is a positive modulator of oligodendrocyte precursor cell differentiation and myelination.

Authors: Hou, Xiaolin  Zhang, Rui  Wang, Junyan  Li, Yunhong  Li, Fan  Zhang, Yan  Zheng, Xiaomin  Shen, Ying  Wang, Yin  Zhou, Liang 
Citation: Hou X, etal., Mol Med Rep. 2018 Mar;17(3):4515-4523. doi: 10.3892/mmr.2018.8439. Epub 2018 Jan 17.
RGD ID: 213230158
Pubmed: PMID:29344669   (View Abstract at PubMed)
PMCID: PMC5802228   (View Article at PubMed Central)
DOI: DOI:10.3892/mmr.2018.8439   (Journal Full-text)

Oligodendrocytes (OLs) are myelin-forming cells that are present within the central nervous system. Impaired oligodendrocyte precursor cell (OPC) differentiation into mature OLs is a major cause of demyelination diseases. Therefore, identifying the underlying molecular mechanisms of OPC differentiation is crucial to understand the processes of myelination and demyelination. It has been acknowledged that various extrinsic and intrinsic factors are involved in the control of OPC differentiation; however, the function of ion channels, particularly the voltage‑gated chloride channel (CLC), in OPC differentiation and myelination are not fully understood. The present study demonstrated that CLC‑2 may be a positive modulator of OPC differentiation and myelination. Western blotting results revealed that CLC‑2 was expressed in both OPCs and OLs. Furthermore, CLC‑2 currents (ICLC‑2) were recorded in both types of cells. The inhibition of ICLC‑2 by GaTx2, a blocker of CLC‑2, was demonstrated to be higher in OPCs compared with OLs, indicating that CLC‑2 may serve a role in OL differentiation. The results of western blotting and immunofluorescence staining also demonstrated that the expression levels of myelin basic protein were reduced following GaTx2 treatment, indicating that the differentiation of OPCs into OLs was inhibited following CLC‑2 inhibition. In addition, following western blot analysis, it was also demonstrated that the protein expression of the myelin proteins yin yang 1, myelin regulatory factor, Smad‑interacting protein 1 and sex‑determining region Y‑box 10 were regulated by CLC‑2 inhibition. Taken together, the results of the present study indicate that CLC‑2 may be a positive regulator of OPC differentiation and able to contribute to myelin formation and repair in myelin‑associated diseases by controlling the number and open state of CLC-2 channels.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Clcn2Ratpositive regulation of oligodendrocyte differentiation  IMP  RGD 
Clcn2Ratpositive regulation of voltage-gated chloride channel activity  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Clcn2  (chloride voltage-gated channel 2)


Additional Information