Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 1526K) PPT slides of all figures Correction (v163,p189) Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ding, J. Articles by Yang, Y. Search for Related Content PubMed PubMed Citation Articles by Ding, J. Articles by Yang, Y. Social Bookmarking                      What's this?

© The Rockefeller University Press, 0021-9525/2002/8/427 $5.00
The Journal of Cell Biology, Volume 158, Number 3, August 5, 2002 427-433

Microtubule-associated protein 1B

Jianqing Ding, Jia-Jia Liu, Anthony S. Kowal, Timothy Nardine, Priyanka Bhattacharya, Arthur Lee and Yanmin Yang

Department of Neurology, Stanford University School of Medicine, Stanford, CA 94305

Address correspondence to Yanmin Yang, Dept. of Neurology, Stanford University School of Medicine, 1201 Welch Rd., Stanford, CA 94305-5489. Tel.: (650) 736-1032. Fax: (650) 498-6262. E-mail: yanmin.yang{at}stanford.edu

Giant axonal neuropathy (GAN), an autosomal recessive disorder caused by mutations in GAN, is characterized cytopathologically by cytoskeletal abnormality. Based on its sequence, gigaxonin contains an NH₂-terminal BTB domain followed by six kelch repeats, which are believed to be important for protein–protein interactions (Adams, J., R. Kelso, and L. Cooley. 2000. Trends Cell Biol. 10:17–24.). Here, we report the identification of a neuronal binding partner of gigaxonin. Results obtained from yeast two-hybrid screening, cotransfections, and coimmunoprecipitations demonstrate that gigaxonin binds directly to microtubule-associated protein (MAP)1B light chain (LC; MAP1B-LC), a protein involved in maintaining the integrity of cytoskeletal structures and promoting neuronal stability. Studies using double immunofluorescent microscopy and ultrastructural analysis revealed physiological colocalization of gigaxonin with MAP1B in neurons. Furthermore, in transfected cells the specific interaction of gigaxonin with MAP1B is shown to enhance the microtubule stability required for axonal transport over long distance. At least two different mutations identified in GAN patients (Bomont, P., L. Cavalier, F. Blondeau, C. Ben Hamida, S. Belal, M. Tazir, E. Demir, H. Topaloglu, R. Korinthenberg, B. Tuysuz, et al. 2000. Nat. Genet. 26:370–374.) lead to loss of gigaxonin–MAP1B-LC interaction. The devastating axonal degeneration and neuronal death found in GAN patients point to the importance of gigaxonin for neuronal survival. Our findings may provide important insights into the pathogenesis of neurodegenerative disorders related to cytoskeletal abnormalities.

Key Words: gigaxonin; MAP1B; cytoskeletal organization; giant axonal neuropathy; protein–protein interaction

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Cleveland, D. W., Yamanaka, K., Bomont, P. (2009). Gigaxonin controls vimentin organization through a tubulin chaperone-independent pathway. Hum Mol Genet 18: 1384-1394 [Abstract] [Full Text]  
• Spiliotis, E. T., Hunt, S. J., Hu, Q., Kinoshita, M., Nelson, W. J. (2008). Epithelial polarity requires septin coupling of vesicle transport to polyglutamylated microtubules. JCB 180: 295-303 [Abstract] [Full Text]  
• Lerch-Gaggl, A. F., Sun, K., Duncan, S. A. (2007). Light Chain 1 of Microtubule-associated Protein 1B Can Negatively Regulate the Action of Pes1. J. Biol. Chem. 282: 11308-11316 [Abstract] [Full Text]  
• Liu, J.-J., Ding, J., Wu, C., Bhagavatula, P., Cui, B., Chu, S., Mobley, W. C., Yang, Y. (2007). Retrolinkin, a membrane protein, plays an important role in retrograde axonal transport. Proc. Natl. Acad. Sci. USA 104: 2223-2228 [Abstract] [Full Text]  
• Ding, J., Allen, E., Wang, W., Valle, A., Wu, C., Nardine, T., Cui, B., Yi, J., Taylor, A., Jeon, N. L., Chu, S., So, Y., Vogel, H., Tolwani, R., Mobley, W., Yang, Y. (2006). Gene targeting of GAN in mouse causes a toxic accumulation of microtubule-associated protein 8 and impaired retrograde axonal transport. Hum Mol Genet 15: 1451-1463 [Abstract] [Full Text]  
• Demir, E, Bomont, P, Erdem, S, Cavalier, L, Demirci, M, Kose, G, Muftuoglu, S, Cakar, A N, Tan, E, Aysun, S, Topcu, M, Guicheney, P, Koenig, M, Topaloglu, H (2005). Giant axonal neuropathy: clinical and genetic study in six cases. J. Neurol. Neurosurg. Psychiatry 76: 825-832 [Abstract] [Full Text]  
• da Cruz, A. B., Schwarzel, M., Schulze, S., Niyyati, M., Heisenberg, M., Kretzschmar, D. (2005). Disruption of the MAP1B-related Protein FUTSCH Leads to Changes in the Neuronal Cytoskeleton, Axonal Transport Defects, and Progressive Neurodegeneration in Drosophila. Mol. Biol. Cell 16: 2433-2442 [Abstract] [Full Text]  
• Reid, E., Connell, J., Edwards, T. L., Duley, S., Brown, S. E., Sanderson, C. M. (2005). The hereditary spastic paraplegia protein spastin interacts with the ESCRT-III complex-associated endosomal protein CHMP1B. Hum Mol Genet 14: 19-38 [Abstract] [Full Text]  
• Bruno, C., Bertini, E., Federico, A., Tonoli, E., Lispi, M. L., Cassandrini, D., Pedemonte, M., Santorelli, F. M., Filocamo, M., Dotti, M. T., Schenone, A., Malandrini, A., Minetti, C. (2004). Clinical and molecular findings in patients with giant axonal neuropathy (GAN). Neurology 62: 13-16 [Abstract] [Full Text]  
• Liu, J.-J., Ding, J., Kowal, A. S., Nardine, T., Allen, E., Delcroix, J.-D., Wu, C., Mobley, W., Fuchs, E., Yang, Y. (2003). BPAG1n4 is essential for retrograde axonal transport in sensory neurons. JCB 163: 223-229 [Abstract] [Full Text]  
• Opal, P., Garcia, J. J., Propst, F., Matilla, A., Orr, H. T., Zoghbi, H. Y. (2003). Mapmodulin/Leucine-rich Acidic Nuclear Protein Binds the Light Chain of Microtubule-associated Protein 1B and Modulates Neuritogenesis. J. Biol. Chem. 278: 34691-34699 [Abstract] [Full Text]  
• Bomont, P., Koenig, M. (2003). Intermediate filament aggregation in fibroblasts of giant axonal neuropathy patients is aggravated in non dividing cells and by microtubule destabilization. Hum Mol Genet 12: 813-822 [Abstract] [Full Text]  
• Uchida, Y. (2003). Overexpression of Full-length but Not N-terminal Truncated Isoform of Microtubule-associated Protein (MAP) 1B Accelerates Apoptosis of Cultured Cortical Neurons. J. Biol. Chem. 278: 366-371 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents