PXD075183 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| 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 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2026-03-03 22:14:42 | ID requested | |
| ⏵ 1 | 2026-04-29 07:26:09 | announced | |
Publication List
| 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] |
Keyword List
| submitter keyword: Parkinson’s disease |
| LRRK2 |
| Rab12 KO |
| Mouse |
| Proteomics;striatal synaptosome |
Contact List
| 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 | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD075183
- Label: PRIDE project
- Name: Disruption of LRRK2 Activator RAB12 Facilitates Neurotransmission and Causes Hyperactivity in Mice
