PXD075183

PXD075183 is an original dataset announced via ProteomeXchange.

Title	Disruption of LRRK2 Activator RAB12 Facilitates Neurotransmission and Causes Hyperactivity in Mice
Description	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.
HostingRepository	PRIDE
AnnounceDate	2026-04-29
AnnouncementXML	Submission_2026-04-29_07:26:08.641.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xue Zhang
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-03 22:14:42	ID requested
⏵ 1	2026-04-29 07:26:09	announced

10.1038/s41531-026-01353-4;

Li X, Chen Y, Wang H, Zhang X, Guiberson NGL, Li X, Burr, é J, Peng J, Zhang H, Yue Z, Disruption of the LRRK2 substrate RAB12 facilitates neurotransmission and causes hyperactivity in mice. NPJ Parkinsons Dis, ():(2026) [pubmed]

submitter keyword: Parkinson’s disease

LRRK2

Rab12 KO

Mouse

Proteomics;striatal synaptosome

Junmin Peng
contact affiliation	Departments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
contact email	junmin.peng@stjude.org
lab head
Xue Zhang
contact affiliation	St. Jude Children's Research Hospital
contact email	xzhang56@stjude.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD075183
     1. Label: PRIDE project
     2. Name: Disruption of LRRK2 Activator RAB12 Facilitates Neurotransmission and Causes Hyperactivity in Mice