Dataset Information

Disruption of LRRK2 Activator RAB12 Facilitates Neurotransmission and Causes Hyperactivity in Mice

ABSTRACT: RAB12 is a family member of small GTPases best known as a physiological substrate of LRRK2 kinase, the variants of which cause Parkinson’s disease (PD). RAB12 - LRRK2 interaction is crucial for the activation of LRRK2 kinase activity and pathogenic signaling in ciliogenesis and immune response. However, the function of RAB12 in neuronal activity and in vivo remains largely unexplored. Here we describe the consequence of Rab12 knock-out (KO) in mice and the role of RAB12 in regulating synaptic trafficking in neurons. Rab12 KO mice developed normally but exhibited enhanced locomotor activity in adulthood. Measuring electrophysiologic properties of Rab12 KO brain slices showed an increased release probability of presynaptic vesicles in excitatory neurons. Live-cell imaging of cortical neurons revealed that Rab12 deletion facilitated, while Rab12 overexpression inhibited, synaptic vesicle exocytosis. Further, proteomic analysis of the Rab12 KO striatum revealed the role of RAB12 in synaptic membrane transport and regulation of synaptic pathways. Collectively, our findings show that the neuronal functions of RAB12 and LRRK2 converge on the regulation of synaptic vesicle traffic, the dysfunction of which is linked to early pathological events in PD.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Xue Zhang

LAB HEAD: Junmin Peng

PROVIDER: PXD075183 | Pride | 2026-04-29

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	2023-11-20-decoys-mouse_ft_mc2_c57.fasta.fas	Fasta
	CP_ZHENYU_FRAC1.1.pepXML	Pepxml
	CP_ZHENYU_FRAC1.mzXML	Mzxml
	CP_ZHENYU_FRAC1.raw	Raw
	CP_ZHENYU_FRAC10.1.pepXML	Pepxml

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Publications

Disruption of the LRRK2 substrate RAB12 facilitates neurotransmission and causes hyperactivity in mice.

Li Xingjian X Chen Yuanxin Y Wang Huaixing H Zhang Xue X Guiberson Noah Guy Lewis NGL Li Xianting X Burré Jacqueline J Peng Junmin J Zhang Hui H Yue Zhenyu Z

NPJ Parkinson's disease 20260424

RAB12 is a small GTPase and a validated substrate of LRRK2, a kinase genetically linked to Parkinson's disease (PD). While RAB12-LRRK2 signaling has been implicated in ciliogenesis and immune regulation, the neuronal function of RAB12 remains largely unexplored. Here, we investigated the role of RAB12 in synaptic physiology using Rab12 knockout (KO) mice. Rab12 KO mice developed normally but exhibited increased locomotor activity in adulthood. Electrophysiological recordings from striatal slices ...[more]

PMID: 42031745

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