BPAG1n4 is essential for retrograde axonal transport in sensory neurons.
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.
Liu
Jia-Jia
JJ
Department of Neurology, Stanford University School of Medicine, Stanford, CA 94305-5489, USA. yanmin.yang@stanford.edu
Ding
Jianqing
J
Kowal
Anthony S
AS
Nardine
Timothy
T
Allen
Elizabeth
E
Delcroix
Jean-Dominique
JD
Wu
Chengbiao
C
Mobley
William
W
Fuchs
Elaine
E
Yang
Yanmin
Y
D000818:Animals; D000831:Animals, Newborn; D001324:Autoantigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D001370:Axonal Transport / Q000235:genetics*; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D019556:COS Cells; D002352:Carrier Proteins; D002522:Chlorocebus aethiops; D003094:Collagen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D003598:Cytoskeletal Proteins; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism / Q000648:ultrastructure; D000071821:Dystonin; D005727:Ganglia, Spinal / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism / Q000648:ultrastructure; D041681:NIH 3T3 Cells; D009419:Nerve Tissue Proteins; D009475:Neurons, Afferent / Q000378:metabolism* / Q000648:ultrastructure; D024041:Non-Fibrillar Collagens; D010391:Pemphigoid, Bullous / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D017434:Protein Structure, Tertiary; D000097805:Collagen Type XVII
D001324:Autoantigens; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D000072159:Dynactin Complex; D004398:Dyneins; D000071821:Dystonin; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D020033:Protein Isoforms; D000097805:Collagen Type XVII; C095667:Dst protein, mouse