Anti-LRRK2 Antibody Picoband® Fluoro550 Conjugated

Leucine-rich repeat kinase 2 (LRRK2), also known as dardarin, is anenzyme that in humans is encoded by the PARK8 gene. It is a member of the leucine-rich repeat kinase family. This gene is mapped to 12q12. The protein is present largely in the cytoplasm but also associates with the mitochondrial outer membrane. Expression of mutant LRRK2 induced apoptotic cell death in neuroblastoma cells and in mouse cortical neurons. It has been determined that LRRK2 possesses mixed-lineage kinase activity, and LRRK2 also showed autophosphorylation activity. What’s more, LRRK2 has an affinity for lipids or lipid-associated proteins and may play a role in the biogenesis or regulation of membranous intracellular structures in the brain. It is also an IFNG target gene that may be involved in signaling pathways relevant to Crohn disease.

Expressed in the brain. Expressed in pyramidal neurons in all cortical laminae of the visual cortex, in neurons of the substantia nigra pars compacta and caudate putamen (at protein level) . Expressed throughout the adult brain, but at a lower level than in heart and liver. Also expressed in placenta, lung, skeletal muscle, kidney and pancreas. In the brain, expressed in the cerebellum, cerebral cortex, medulla, spinal cord occipital pole, frontal lobe, temporal lobe and putamen. Expression is particularly high in brain dopaminoceptive areas. .

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. Regulates neuronal process morphology in the intact central nervous system (CNS) . Plays a role in synaptic vesicle trafficking. Phosphorylates PRDX3. Has GTPase activity. May play a role in the phosphorylation of proteins central to Parkinson disease. .

1. Biskup, S., Moore, D. J., Celsi, F., Higashi, S. West, A. B., Andrabi, S. A., Kurkinen, K., Yu, S.-W., Savitt, J. M., Waldvogel, H. J., Faull, R. L. M., Emson, P. C., Torp, R., Ottersen, O. P., Dawson, T. M., Dawson, V. L. Localization of LRRK2 to membranous and vesicular structures in mammalian brain. Ann. Neurol. 60: 557-569, 2006. 2. Paisán-Ruíz C, Jain S, Evans EW, Gilks WP, Simón J, van der Brug M, López de Munain A, Aparicio S, Gil AM, Khan N, Johnson J, Martinez JR, Nicholl D, Carrera IM, Pena AS, de Silva R, Lees A, Martí-Massó JF, Pérez-Tur J, Wood NW, Singleton AB (November 2004) . Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 44 (4) : 595–600. 3. West, A. B., Moore, D. J., Biskup, S., Bugayenko, A., Smith, W. W., Ross, C. A., Dawson, V. L., Dawson, T. M. Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc. Nat. Acad. Sci. 102: 16842-16847, 2005.

Membrane; Peripheral membrane protein. Cytoplasm. Perikaryon. Mitochondrion. Golgi apparatus. Cell projection, axon. Cell projection, dendrite. Endoplasmic reticulum . Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . Endosome . Lysosome . Mitochondrion outer membrane . Mitochondrion inner membrane . Mitochondrion matrix . Predominantly associated with intracytoplasmic vesicular and membranous structures (By similarity) . Localized in the cytoplasm and associated with cellular membrane structures. Predominantly associated with the mitochondrial outer membrane of the mitochondria. Colocalized with RAB29 along tubular structures emerging from Golgi apparatus. Localizes in intracytoplasmic punctate structures of neuronal perikarya and dendritic and axonal processes. .