The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
Localization of LRRK2 to membranous and vesicular structures in mammalian brain
Abstract
Objective: The PARK8 gene responsible for late‐onset autosomal dominant Parkinson's disease encodes a large novel protein of unknown biological function termed leucine‐rich repeat kinase 2 (LRRK2). The studies herein explore the localization of LRRK2 in the mammalian brain. Methods: Polyclonal antibodies generated against the amino or carboxy termini of LRRK2 were used to examine the biochemical, subcellular, and immunohistochemical distribution of LRRK2. Results: LRRK2 is detected in rat brain as an approximate 280kDa protein by Western blot analysis. Subcellular fractionation demonstrates the presence of LRRK2 in microsomal, synaptic vesicle–enriched and synaptosomal cytosolic fractions from rat brain, as well as the mitochondrial outer membrane. Immunohistochemical analysis of rat and human brain tissue and primary rat cortical neurons, with LRRK2‐specific antibodies, shows widespread neuronal‐specific labeling localized exclusively to punctate structures within perikarya, dendrites, and axons. Confocal colocalization analysis of primary cortical neurons shows partial yet significant overlap of LRRK2 immunoreactivity with markers specific for mitochondria and lysosomes. Furthermore, ultrastructural analysis in rodent basal ganglia detects LRRK2 immunoreactivity associated with membranous and vesicular intracellular structures, including lysosomes, endosomes, transport vesicles, and mitochondria. Interpretation: The association of LRRK2 with a variety of membrane and vesicular structures, membrane‐bound organelles, and microtubules suggests an affinity of LRRK2 for lipids or lipid‐associated proteins and may suggest a potential role in the biogenesis and/or regulation of vesicular and membranous intracellular structures within the mammalian brain. Ann Neurol 2006;60:557–569
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Mutations in LRRK2 Cause Autosomal-Dominant Parkinsonism with Pleomorphic Pathology
Zimprich, A., Biskup, S., Leitner, P., Lichtner, P., Farrer, M., Lincoln, S., Kachergus, J., Hulihan, M., Uitti, R. J., Calne, D. B., et al. (2004) · Neuron · doi:10.1016/j.neuron.2004.11.005 · Cited by 3,005
Self-citationCloning of the Gene Containing Mutations that Cause PARK8-Linked Parkinson's Disease
Paisán-Ruı́z, C., Jain, S., Evans, E. W., Gilks, W. P., Simón, J., van der Brug, M., de Munain, A. L., Aparicio, S., Gil, A. M., Khan, N., et al. (2004) · Neuron · doi:10.1016/j.neuron.2004.10.023 · Cited by 2,405
MOLECULAR PATHOPHYSIOLOGY OF PARKINSON'S DISEASE
Moore, D. J., West, A. B., Dawson, V. L., & Dawson, T. M. (2005) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.28.061604.135718 · Cited by 1,280
Self-citationParkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity
West, A. B., Moore, D. J., Biskup, S., Bugayenko, A., Smith, W. W., Ross, C. A., Dawson, V. L., & Dawson, T. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507360102 · Cited by 1,228
Self-citationMechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures
Dawson, V., Dawson, T., Bartley, D., Uhl, G., & Snyder, S. (1993) · The Journal of Neuroscience · doi:10.1523/jneurosci.13-06-02651.1993 · Cited by 1,014
Self-citationChung, K. K. K., Zhang, Y., Lim, K. L., Tanaka, Y., Huang, H., Gao, J., Ross, C. A., Dawson, V. L., & Dawson, T. M. (2001) · Nature Medicine · doi:10.1038/nm1001-1144 · Cited by 750
Self-citationDifferent modes of expression of AMPA and NMDA receptors in hippocampal synapses
Takumi, Y., Ramírez-León, V., Laake, P., Rinvik, E., & Ottersen, O. P. (1999) · Nature Neuroscience · doi:10.1038/10172 · Cited by 675
Self-citationA new locus for Parkinson's disease (PARK8) maps to chromosome 12p11.2–q13.1
Funayama, M., Hasegawa, K., Kowa, H., Saito, M., Tsuji, S., & Obata, F. (2002) · Annals of Neurology · doi:10.1002/ana.10113 · Cited by 667
Specificity and regulation of a synaptic vesicle docking complex
Pevsner, J., Hsu, S.-C., Braun, J. E. A., Calakos, N., Ting, A. E., Bennett, M. K., & Scheller, R. H. (1994) · Neuron · doi:10.1016/0896-6273(94)90352-2 · Cited by 592
The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity
Gloeckner, C. J., Kinkl, N., Schumacher, A., Braun, R. J., O'Neill, E., Meitinger, T., Kolch, W., Prokisch, H., & Ueffing, M. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddi439 · Cited by 477
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The Role of Oxidative Stress in Parkinson's Disease
Dias, V., Junn, E., & Mouradian, M. M. (2013) · Journal of Parkinson’s Disease · doi:10.3233/jpd-130230 · Cited by 1,845
Mitochondrial dysfunction and oxidative stress in Parkinson's disease
Subramaniam, S. R., & Chesselet, M.-F. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.04.004 · Cited by 913
Parkinson’s disease: genetics and pathogenesis
Shulman, J. M., De Jager, P. L., & Feany, M. B. (2011) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130242 · Cited by 801
Thomas, B., & Beal, M. F. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm159 · Cited by 748
Mitochondrial Defects and Oxidative Stress in Alzheimer Disease and Parkinson Disease
Yan, M. H., Wang, X., & Zhu, X. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.11.014 · Cited by 718
Metadata
- Authors
- Biskup, S., Moore, D. J., Celsi, F., Higashi, S., West, A. B., Andrabi, S. A., Kurkinen, K., Yu, S., Savitt, J. M., Waldvogel, H. J., Faull, R. L. M., Emson, P. C., Torp, R., Ottersen, O. P., Dawson, T. M., & Dawson, V. L.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2006-11
- Volume
- 60
- Issue
- 5
- Pages
- 557-569
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2031031932
- Cited by
- 511
- References
- 22
- FWCI
- 18.82
- Type
- journal article
- Language
- en
- Open access
- closed
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- Biskup, S., Moore, D. J., Celsi, F., Higashi, S., West, A. B., Andrabi, S. A., Kurkinen, K., Yu, S., Savitt, J. M., Waldvogel, H. J., Faull, R. L. M., Emson, P. C., Torp, R., Ottersen, O. P., Dawson, T. M., & Dawson, V. L. (2006). Localization of LRRK2 to membranous and vesicular structures in mammalian brain. Annals of Neurology. https://doi.org/10.1002/ana.21019
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