Experimental Neurobiology

Summary of studies on the relationship between LRRK2 and ciliogenesis

Study	Tissue or cell line	Targets investigated	Cilia marker	Ciliogenesis change by the treatments	Reference
Previous	A549, RPE	Rab10KO	Arl13B	↑ by Rab10KO*	14

	MEF-LRRK2-R1441G	MLi-2 treatment and Rab10KD		↑ by MLi-2* and by Rab10KD*

	IPS cells	LRRK2^WT/WT vs LRRK2^G2019S/WT		↓ in LRRK2^G2019S/WT

	LRRK2^G2019S/WT IPS cells	MLi-2 treatment		↑ by MLi-2*

	Neurons in the cortex	WT/WT vs R1441C/R1441C	SSTR	↓ in LRRK2^{R1441C/R1441C}*

	Cholinergic neurons in the striatum		AC3	↓ in LRRK2^{R1441C/R1441C}

	Non-cholinergic neurons in the striatum			– by MLi-2

	HEK 293 cells transfected with vector or LRRK2 WT	MLi-2 treatment	PT	– by MLi-2	17

	HEK 293 cells expressing LRRK2 G2019S, R1441C, Y1699C			↑ by MLi-2^#

	Human fibroblast	LRRK2 WT vs G2019S		↓ in LRRK2^G2019S/WT*

	WT & G2019S human fibroblast	MLi-2 treatment	PT	– by MLi-2

	WT primary astrocytes		Arl13B	– by MLi-2

	G2019S KI primary astrocytes			↑ by MLi-2^#

	SH-SY5Y	Differentiation	AT	↑ by differentiation	39

	SH-SY5Y (both differentiated and undifferentiated)	MG132 treatment		↓ by MG132*

	Undifferentiated SH-SY5Y	α-synuclein WT, A30P, A53T expression		↓ by α-synuclein expression*

	SH-SY5Y	Rotenone, MPP⁺ treatment	Arl13B	↑ by treatments^#	20

	MEF	Scrambled shRNA	Arl13B	– by Mli-2**	15

	MEF-LRRK2-R1441C	MLi-2 treatment	SSTR3-GFP	↑ by MLi-2*	16

	MEF-LRRK2-R1441G KI	MLi-2 treatment	Arl13B	↑ by MLi-2*	11

	NIH3T3 transfected with LRRK2 G2019S

Our study	Rat cortical/ hippocampal WT primary neurons	GSK/MLi-2 treatment	Arl13B	– by treatment	This study

	Fibroblasts (LRRK2^G2019S/WT)	MLi-2 treatment		– by MLi-2

	Fibroblasts (LRRK2^WT/WT vs LRRK2^G2019S/WT)	LRRK2^WT/WT vs LRRK2^G2019S/WT		↑ in LRRK2^G2019S/WT##

	NSCs (LRRK2^WT/WT vs LRRK2^G2019S/WT)			↑ in LRRK2^G2019S/WT##

	Murine cortical primary neurons			– between genotypes

	Isogenic pairs of iPSCs and NSCs (LRRK2^WT/WT vs LRRK2^G2019S/WT)	LRRK2^WT/WT vs LRRK2^G2019S/WT		– between genotypes

		MLi-2 treatment		– by MLi-2

Differentiated SH-SY5Y	MLi-2 treatment	Slightly ↑ by MLi-2^##

	Rab10 WT expression	– by expression

–, little change; KI, Knock-in; AC3, adenylate cyclase 3; AT, acetylated tubulin; PT, polyglutamylated tubulin; SSTR, somatostatin receptor.

*Statistically significant change.

**The result was observed in the control sample (scrambled shRNA) to test effect of PPM1H knockdown on ciliogenesis.

^#Statistically significant change was observed only under normal serum-fed condition, but not in the serum starved condition.

^##Significant change regardless of serum condition.

Exp Neurobiol 2021;30:232~243 https://doi.org/10.5607/en21003