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Published 27 October 2003. doi:10.1083/jcb.200306075
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© The Rockefeller University Press, 0021-9525/2003/10/223 $8.00
The Journal of Cell Biology, Volume 163, Number 2, 223-229

Article

BPAG1n4 is essential for retrograde axonal transport in sensory neurons



Jia-Jia Liu1, Jianqing Ding1, Anthony S. Kowal1, Timothy Nardine1, Elizabeth Allen1, Jean-Dominique Delcroix1, Chengbiao Wu1, William Mobley1, Elaine Fuchs2 and Yanmin Yang1

1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305
2 Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10021

Address correspondence to Yanmin Yang, Department of Neurology, Stanford University School of Medicine, 1201 Welch Rd., MSLS P207, Stanford, CA 94305-5489. Tel.: (650) 736-1032. Fax: (650) 498-6262. email: yanmin.yang{at}stanford.edu

Disruption of the BPAG1 (bullous pemphigoid antigen 1) gene results in progressive deterioration in motor function and devastating sensory neurodegeneration in the null mice. We have previously demonstrated that BPAG1n1 and BPAG1n3 play important roles in organizing cytoskeletal networks in vivo. Here, we characterize functions of a novel BPAG1 neuronal isoform, BPAG1n4. Results obtained from yeast two-hybrid screening, blot overlay binding assays, and coimmunoprecipitations demonstrate that BPAG1n4 interacts directly with dynactin p150Glued through its unique ezrin/radixin/moesin domain. Studies using double immunofluorescent microscopy and ultrastructural analysis reveal physiological colocalization of BPAG1n4 with dynactin/dynein. Disruption of the interaction between BPAG1n4 and dynactin results in severe defects in retrograde axonal transport. We conclude that BPAG1n4 plays an essential role in retrograde axonal transport in sensory neurons. These findings might advance our understanding of pathogenesis of axonal degeneration and neuronal death.

Key Words: cytoskeleton; BPAG1n4–dynactin interaction; axonal transport; neurodegeneration; ERM domain

Abbreviations used in this paper: BPAG1, bullous pemphigoid antigen 1; co-IP, coimmunoprecipitation; DRG, dorsal root ganglion; ERM, ezrin/radixin/moesin; immunoEM, immunoelectron microscopy; Tf-TR, transferrin conjugated with Texas red; WT, wild type.


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