2. Academic Validation
  3. Ciliogenesis is Not Directly Regulated by LRRK2 Kinase Activity in Neurons

Ciliogenesis is Not Directly Regulated by LRRK2 Kinase Activity in Neurons

  • Exp Neurobiol. 2021 Jun 30;30(3):232-243. doi: 10.5607/en21003.
Hyejung Kim 1,  Hyuna Sim 2 3,  Joo-Eun Lee 2,  Mi Kyoung Seo 4,  Juhee Lim 5,  Yeojin Bang 5,  Daleum Nam 1,  Seo-Young Lee 6,  Sun-Ku Chung 7,  Hyun Jin Choi 5,  Sung Woo Park 4 8,  Ilhong Son 1 9,  Janghwan Kim 2 3,  Wongi Seol 1
Affiliations

Affiliations

  • 1 InAm Neuroscience Research Center, Sanbon Medical Center, College of Medicine, Wonkwang University, Gunpo 15865, Korea.
  • 2 Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea.
  • 3 Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology, Daejeon 34141, Korea.
  • 4 Paik Institute for Clinical Research, Inje University College of Medicine, Busan 47392, Korea.
  • 5 College of Pharmacy, CHA University, Seongnam 13496, Korea.
  • 6 Division of Clinical Medicine, Korea Institute of Oriental Medicine, Daejeon 34054, Korea.
  • 7 Division of Herbal Medicine Research, Korea Institute of Oriental Medicine, Daejeon 34054, Korea.
  • 8 Department of Convergence Biomedical Science, Inje University College of Medicine, Busan 47392, Korea.
  • 9 Department of Neurology, Sanbon Medical Center, College of Medicine, Wonkwang University, Gunpo 15865, Korea.
PMID: 34230223 DOI: 10.5607/en21003
Abstract

Mutations in the Leucine-rich repeat kinase 2 (LRRK2) gene are the most prevalent cause of familial Parkinson's disease (PD). The increase in LRRK2 kinase activity observed in the pathogenic G2019S mutation is important for PD development. Several studies have reported that increased LRRK2 kinase activity and treatment with LRRK2 kinase inhibitors decreased and increased ciliogenesis, respectively, in mouse embryonic fibroblasts (MEFs) and retinal pigment epithelium (RPE) cells. In contrast, treatment of SH-SY5Y dopaminergic neuronal cells with PD-causing chemicals increased ciliogenesis. Because these reports were somewhat contradictory, we tested the effect of LRRK2 kinase activity on ciliogenesis in neurons. In SH-SY5Y cells, LRRK2 Inhibitor treatment slightly increased ciliogenesis, but serum starvation showed no increase. In rat primary neurons, LRRK2 Inhibitor treatment repeatedly showed no significant change. Little difference was observed between primary cortical neurons prepared from wild-type (WT) and G2019S+/- mice. However, a significant increase in ciliogenesis was observed in G2019S+/- compared to WT human fibroblasts, and this pattern was maintained in neural stem cells (NSCs) differentiated from the induced pluripotent stem cells (iPSCs) prepared from the same WT/G2019S fibroblast pair. NSCs differentiated from G2019S and its gene-corrected WT counterpart iPSCs were also used to test ciliogenesis in an isogenic background. The results showed no significant difference between WT and G2019S regardless of kinase inhibitor treatment and B27-deprivation-mimicking serum starvation. These results suggest that LRRK2 kinase activity may be not a direct regulator of ciliogenesis and ciliogenesis varies depending upon the cell type or genetic background.

Keywords

Ciliogenesis; LRRK2 kinase; Neuron; Parkinson’s disease; Primary cilia.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z