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The Journal of Neuroscience, October 15, 2003, 23(28):9452-9458

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Cellular/Molecular
Neurofilament Transport In Vivo Minimally Requires Hetero-Oligomer Formation

Aidong Yuan,^1,2 Mala V. Rao,^1,2 Asok Kumar,^1,2 Jean-Pierre Julien,⁴ and Ralph A. Nixon^1,2,3

¹Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962, Departments of ²Psychiatry and ³Cell Biology, New York University School of Medicine, New York, New York 10016, and ⁴Center for Research in Neurosciences, McGill University, Research Institute of the McGill University Health Center, Montreal, Quebec, H3G 1A4, Canada

Neurofilament assembly requires at minimum the polymerization of neurofilament light chain (NF-L) with either neurofilament medium chain (NF-M) or neurofilament heavy chain (NF-H) subunits, but requirements for their axonal transport have long been controversial. Using a gene deletion approach, we generated mice containing only NF-L or NF-M. In vivo pulse radiolabeling analyses in retinal ganglion cell neurons revealed that NF-L alone is incapable of efficient transport, whereas nearly one-half of the normal level of NF-M is transported along optic axons in the absence of the other triplet subunits. Under these conditions, however, NF-M transport is completely abolished by deleting -internexin. Our results strongly suggest that efficient neurofilament protein transport in vivo minimally requires hetero-oligomer formation. They also show that NF-M can partner with intermediate filament proteins other than the NF-H and NF-L subunits in neurons to support slow transport and possibly other functions of neuronal intermediate filaments.

Key words: neurofilaments; neurofilament medium subunit; neurofilament light subunit; -internexin; hetero-oligomer; slow axonal transport; optic axons; knock-out mice; intermediate filaments; cytoskeletal protein

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Received March 11, 2003; revised August 19, 2003; accepted August 20, 2003.

This article has been cited by other articles:

				A. Yuan, T. Sasaki, M. V. Rao, A. Kumar, V. Kanumuri, D. S. Dunlop, R. K. Liem, and R. A. Nixon Neurofilaments Form a Highly Stable Stationary Cytoskeleton after Reaching a Critical Level in Axons J. Neurosci., September 9, 2009; 29(36): 11316 - 11329. [Abstract] [Full Text] [PDF]

				A. Yuan, A. Kumar, C. Peterhoff, K. Duff, and R. A. Nixon Axonal Transport Rates In Vivo Are Unaffected by Tau Deletion or Overexpression in Mice J. Neurosci., February 13, 2008; 28(7): 1682 - 1687. [Abstract] [Full Text] [PDF]

				S. Millecamps, G. Gowing, O. Corti, J. Mallet, and J.-P. Julien Conditional NF-L Transgene Expression in Mice for In Vivo Analysis of Turnover and Transport Rate of Neurofilaments J. Neurosci., May 2, 2007; 27(18): 4947 - 4956. [Abstract] [Full Text] [PDF]

				A. Yuan, M. V. Rao, T. Sasaki, Y. Chen, A. Kumar, Veeranna, R. K. H. Liem, J. Eyer, A. C. Peterson, J.-P. Julien, et al. {alpha}-Internexin Is Structurally and Functionally Associated with the Neurofilament Triplet Proteins in the Mature CNS J. Neurosci., September 27, 2006; 26(39): 10006 - 10019. [Abstract] [Full Text] [PDF]

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