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The Journal of Neuroscience, May 14, 2008, 28(20):5248-5256; doi:10.1523/JNEUROSCI.0309-08.2008

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Cellular/Molecular
Cytoskeletal Requirements in Axonal Transport of Slow Component-b

Subhojit Roy,^1,2 Matthew J. Winton,¹ Mark M. Black,⁴ John Q. Trojanowski,^1,2,3 and Virginia M.-Y. Lee^1,2,3

¹Center for Neurodegenerative Disease Research, ²Department of Pathology and Laboratory Medicine, and ³Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, and ⁴Department of Anatomy and Cell Biology, Temple University Hospital, Philadelphia, Pennsylvania 19130

Correspondence should be addressed to Dr. Virginia M.-Y. Lee, Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 3600 Spruce Street, 3rd floor, Maloney Building, Philadelphia, PA 19104. Email: vmylee{at}mail.med.upenn.edu

Slow component-b (SCb) translocates 200 diverse proteins from the cell body to the axon and axon tip at average rates of 2–8 mm/d. Several studies suggest that SCb proteins are cotransported as one or more macromolecular complexes, but the basis for this cotransport is unknown. The identification of actin and myosin in SCb led to the proposal that actin filaments function as a scaffold for the binding of other SCb proteins and that transport of these complexes is powered by myosin: the "microfilament-complex" model. Later, several SCb proteins were also found to bind F-actin, supporting the idea, but despite this, the model has never been directly tested. Here, we test this model by disrupting the cytoskeleton in a live-cell model system wherein we directly visualize transport of SCb cargoes. We focused on three SCb proteins that we previously showed were cotransported in our system: -synuclein, synapsin-I, and glyceraldehyde-3-phosphate dehydrogenase. Disruption of actin filaments with latrunculin had no effect on the velocity or frequency of transport of these three proteins. Furthermore, cotransport of these three SCb proteins continued in actin-depleted axons. We conclude that actin filaments do not function as a scaffold to organize and transport these and possibly other SCb proteins. In contrast, depletion of microtubules led to a dramatic inhibition of vectorial transport of SCb cargoes. These findings do not support the microfilament-complex model, but instead indicate that the transport of protein complexes in SCb is powered by microtubule motors.

Key words: axonal transport; slow transport; slow component-b; -synuclein; synapsin-I; protein complexes

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Received Jan. 23, 2008; revised March 23, 2008; accepted April 9, 2008.

Correspondence should be addressed to Dr. Virginia M.-Y. Lee, Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 3600 Spruce Street, 3rd floor, Maloney Building, Philadelphia, PA 19104. Email: vmylee{at}mail.med.upenn.edu

This article has been cited by other articles:

				I. Tint, D. Jean, P. W. Baas, and M. M. Black Doublecortin Associates with Microtubules Preferentially in Regions of the Axon Displaying Actin-Rich Protrusive Structures J. Neurosci., September 2, 2009; 29(35): 10995 - 11010. [Abstract] [Full Text] [PDF]

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