Phospho-Rab12 (Ser106) (F4C6L) Rabbit Monoclonal Antibody #45036

Rab12, a member of the Ras superfamily of small Rab GTPases, localizes to the trans-Golgi network (TGN), endosomes, and lysosomes to regulate various cellular protein trafficking. Reported protein trafficking functions of Rab12 include transporting the epidermal growth factor receptor (EGFR) from the TGN to the plasma membrane and transporting the transferrin receptor (TfR) from recycling endosomes to lysosomes (1-3). Rab12 is both a regulator and a substrate of Leucine-rich repeat kinase 2 (LRRK2). It recruits LRRK2 to the lysosomal membrane in response to damage, which enhances kinase activity and promotes Rab10 phosphorylation (4). In addition to its role in lysosomal damage response, the Rab12-LRRK2 complex regulates ciliary and centrosome homeostasis in the brain. As a substrate, Rab12 is phosphorylated by LRRK2 within its switch-II domain at Ser106. LRRK2 mutations associated with Parkinson's disease (PD), as well as the VPS35 D620N mutation linked to PD that lies upstream of LRRK2, drive kinase hyperactivity, increasing Rab12 phosphorylation (5-8). This phosphorylation site is a suggested blood-based biomarker for patients with a G2019S LRRK2 mutation (9). Elevated Rab12 phosphorylation at Ser106 is also observed in the brain of patients diagnosed with PD, dementia with Lewy bodies (DLB), Alzheimer’s disease (AD), Pick’s disease, progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD) (10).