LRRK2, EnkiLife, AMRe13446

LRRK2 positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway. The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes. Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose 6 phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner. Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, autophagy, and vesicle trafficking (PubMed: 20949042, PubMed: 22012985, PubMed: 26824392, PubMed: 29125462, PubMed: 28720718, PubMed: 29127255, PubMed: 30398148, PubMed: 29212815, PubMed: 30635421, PubMed: 21850687, PubMed: 23395371, PubMed: 17114044, PubMed: 24687852, PubMed: 26014385, PubMed: 25201882). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed: 26824392, PubMed: 28720718, PubMed: 29127255, PubMed: 30398148, PubMed: 29212815, PubMed: 29125462, PubMed: 30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB35, and RAB43 (PubMed: 26824392, PubMed: 28720718, PubMed: 29127255, PubMed: 30398148, PubMed: 29212815, PubMed: 29125462, PubMed: 30635421, PubMed: 23395371). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed: 26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr- 72' on RAB8A (PubMed: 26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed: 29125462, PubMed: 30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed: 23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed: 17114044). Plays a role in synaptic vesicle trafficking (PubMed: 24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed: 25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed: 22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed: 22012985). Phosphorylates PRDX3 (PubMed: 21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed: 28720718). Independent of its kinase activity, inhibits the proteosomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed: 26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed: 18230735, PubMed: 26824392, PubMed: 29125462, PubMed: 28720718, PubMed: 29212815).