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. 2023 Oct 27:37:101017.
doi: 10.1016/j.ymgmr.2023.101017. eCollection 2023 Dec.

Defective oligodendrocyte differentiation by hypomyelinating leukodystrophy 13 (HLD13)-associated mutation of Hikeshi

Yuki Miyamoto  1   2 , Kohei Hattori  1 , Junji Yamauchi  1   2   3
Affiliations

Defective oligodendrocyte differentiation by hypomyelinating leukodystrophy 13 (HLD13)-associated mutation of Hikeshi

Yuki Miyamoto et al. Mol Genet Metab Rep. .
No abstract available

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Conflict of interest statement

None. The following are the supplementary data related to this article.Supplementary Fig. S1Hikeshi (C4S or V54L) inhibits heat shock-induced nuclear transport of Hsp70 in rat primary oligodendrocyte precursor cells. (A, B) Oligodendrocyte precursor cells expressing the GFP-tagged Hikeshi proteins were induced to differentiate, treated with or without heat shock, stained with an antibody against GFP (green) or Hsp70 (red), and fixed with Vectashield mounting medium with nuclear DAPI (Blue). Merged images were also depicted. In wild type Hikeshi-expressing cells, Hsp70 was transported into the nucleus with heat shock treatment; in contrast, Hikeshi (C4S or V54L) blocked the transport. Nuclear regions were surrounded white dotted lines. Scale bar indicates 10 μm.Supplementary Fig. S1 Supplementary data to this article can be found online at https://doi.org/10.1016/j.ymgmr.2023.101017.

Figures

Fig. 1
Fig. 1
Expression of the V54L mutant proteins of Hikeshi inhibits differentiation in rat primary oligodendrocyte precursor cells. (A-C) Oligodendrocyte precursor cells were isolated from embryonic day 15 (E15) Sprague-Dawley rats, infected using recombinant retroviruses (wild type [WT] Hikeshi or Hikeshi with the C4S or V54L mutation), and induced to differentiate. The lysates of their cells were subjected into SDS-PAGE and immunoblotted with an anti-MBP, CNPase, Hikeshi, or control actin antibody. Exogenous GFP-tagged Hikeshi proteins were detected with an anti-GFP antibody. Expression of GFP-tagged Hikeshi with the C4S mutation weakly decreased the expression levels of endogenous Hikeshi, suggesting that decreased expression levels of endogenous Hikeshi can affect differentiation. On the other hand, Expression of GFP-tagged Hikeshi with the V54L mutation did not significantly change the expression levels of endogenous Hikeshi, suggesting that its mutation itself may affect differentiation. Immunoreactive protein bands were statistically represented relative to protein bands in cells expressing the wild types (control bands) as 100% in graphs (*** p < 0.001; n = 5 blots). (D-G) Infected oligodendrocyte precursor cells were induced to differentiate and stained with anti-MBP or APC and Olig2 antibodies (red). Differentiating MBP- or APC-positive cells per Olig2-positive cells were represented as percentages in a graph (*** p < 0.001, * p < 0.05; n = 10 fields). Olig2 are expressed throughout all oligodendrocyte lineage cells. Although the efficiencies of differentiated cells such as MBP-positive cells for all Olig2-positive oligodendrocyte lineage cells were not high, Hikeshi with the C4S or V54L mutation indeed inhibited differentiation. Scale bar indicates 20 μm.
Supplementary Fig. S1
Supplementary Fig. S1
Hikeshi (C4S or V54L) inhibits heat shock-induced nuclear transport of Hsp70 in rat primary oligodendrocyte precursor cells. (A, B) Oligodendrocyte precursor cells expressing the GFP-tagged Hikeshi proteins were induced to differentiate, treated with or without heat shock, stained with an antibody against GFP (green) or Hsp70 (red), and fixed with Vectashield mounting medium with nuclear DAPI (Blue). Merged images were also depicted. In wild type Hikeshi-expressing cells, Hsp70 was transported into the nucleus with heat shock treatment; in contrast, Hikeshi (C4S or V54L) blocked the transport. Nuclear regions were surrounded white dotted lines. Scale bar indicates 10 μm.
See this image and copyright information in PMC

References

    1. Vasilescu C., Isohanni P., Palomäki M., Pihko H., Suomalainen A., Carroll C.J. Absence of Hikeshi, a nuclear transporter for heat-shock protein HSP70, causes infantile hypomyelinating leukoencephalopathy. Eur. J. Hum. Genet. 2017;25:366–370. - PMC - PubMed
    1. Hattori K., Tago K., Memezawa S., Ochiai A., Sawaguchi S., Kato Y., Sato T., Tomizuka K., Ooizumi H., Ohbuchi K., Mizoguchi K., Miyamoto Y., Yamauchi J. The infantile leukoencephalopathy-associated mutation of C11ORF73/HIKESHI proteins generates de novo interactive activity with Filamin A, inhibiting oligodendroglial cell morphological differentiation. Medicines. 2021;8:9. - PMC - PubMed
    1. Edvardson S., Kose S., Jalas C., Fattal-Valevski Watanabe A., Ogawa Y., Mamada H., Fedick A.M., Ben-Shachar S., Treff N.R., Shaag A., Bale S., Gärtner J., Imamoto N., Elpeleg O. Leukoencephalopathy and early death associated with an Ashkenazi-Jewish founder mutation in the Hikeshi gene. J. Med. Genet. 2016;53:132–137. - PubMed
    1. Miyamoto Y., Torii T., Terao M., Takada S., Tanoue A., Katoh H., Yamauchi J. Rnd2 differentially regulates oligodendrocyte myelination at different developmental periods. Mol. Biol. Cell. 2021;32:769–787. - PMC - PubMed

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