Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
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Leucine-rich Repeat Kinase 2 (LRRK2) Phosphorylates Rab10 in Glia and Neurons

  • Ho, Dong Hwan (InAm Neuroscience Research Center, Sanbon Medical Center, College of Medicine, Wonkwang University) ;
  • Nam, Daleum (InAm Neuroscience Research Center, Sanbon Medical Center, College of Medicine, Wonkwang University) ;
  • Seo, Mi Kyoung (Paik Institute for Clinical Research, Inje University College of Medicine) ;
  • Park, Sung Woo (Paik Institute for Clinical Research, Inje University College of Medicine) ;
  • Son, Ilhong (InAm Neuroscience Research Center, Sanbon Medical Center, College of Medicine, Wonkwang University) ;
  • Seol, Wongi (InAm Neuroscience Research Center, Sanbon Medical Center, College of Medicine, Wonkwang University)
  • Received : 2019.04.19
  • Accepted : 2019.06.13
  • Published : 2019.06.30
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Abstract

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease (PD). LRRK2 contains a functional kinase and GTPase domains. A pathogenic G2019S mutation that is the most prevalent among the LRRK2 mutations and is also found in sporadic cases, increases its kinase activity. Therefore, identification of LRRK2 kinase substrates and the development of kinase inhibitors are under intensive investigation to find PD therapeutics. Several recent studies have suggested members of Rab proteins, a branch of the GTPase superfamily, as LRRK2 kinase substrates. Rab proteins are key regulators of cellular vesicle trafficking. Among more than 60 members of human Rab proteins, Rab3, Rab5, Rab8, Rab10, Rab12, Rab29, Rab35, and Rab43 have been identified as LRRK2 kinase substrates. However, most studies have used human embryonic kidney (HEK) 293T cells overexpressing LRRK2/Rab proteins or murine embryonic fibroblast (MEF) cells which are not relevant to PD, rather than neuronal cells. In this study, we tested whether Rab proteins are phosphorylated by LRRK2 in astroglia in addition to neurons. Among the various Rab substrates, we tested phosphorylation of Rab10, because of the commercial availability and credibility of the phospho-Rab10 (pRab10) antibody, in combination with a specific LRRK2 kinase inhibitor. Based on the results of specific LRRK2 kinase inhibitor treatment, we concluded that LRRK2 phosphorylates Rab10 in the tested brain cells such as primary neurons, astrocytes and BV2 microglial cells.

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References

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