title: Trafficking of macromolecules and organelles in cultured Dystonia musculorum sensory neurons is normal.
abstract: Dystonia musculorum (dt) mice suffer from a recessive neuropathy characterized by the progressive loss of sensory axons. The gene responsible for this disorder, dystonin/Bpag1, encodes several alternatively spliced forms of a cytoskeletal linker protein. Neural isoforms of dystonin/Bpag1 are predicted to link actin filaments to microtubules. Consistent with this, previous observations have demonstrated that the cytoskeleton within sensory neurites of dt mice is perturbed. Also, recent results have indicated that a neural isoform of dystonin/Bpag1 interacts with the dynein motor complex. Because microtubule organization and dynein motor function are essential for trafficking, we hypothesized that this process would be perturbed in dt sensory neurons. Here, we demonstrate that cultured primary dorsal root ganglion (DRG) neurons express dystonin/Bpag1 and that loss of this expression causes an increase in apoptosis and a decrease in average neurite length. In contrast, detailed examination showed that the organization of microtubules is indistinguishable in DRG neuronal cultures from neonatal dt and wild-type mice. In addition, the steady-state distribution of several molecules and organelles is unchanged in these cultures. Furthermore, the speeds of mitochondrial movement in both anterograde and retrograde directions were comparable in dt and wild-type sensory neurons cultured from neonatal mice. Thus, dystonin/Bpag1 is not essential for microtubule network assembly since the microtubule network is intact in short-term cultures of sensory neurons from neonatal mice lacking this protein. In addition, dystonin/Bpag1 is not an essential part of the dynein motor complex for mitochondrial transport since mitochondrial trafficking is normal in cultured sensory neurons from dt mice.
authors.affiliation: Molecular Medicine Program, Ottawa Health Research Institute, Ottawa, Ontario K1H 8L6, Canada.
authors.forename: Madeline
authors.initials: M
authors.lastname: Pool
authors.forename: Peter
authors.initials: P
authors.lastname: Rippstein
authors.forename: Heidi
authors.initials: H
authors.lastname: McBride
authors.forename: Rashmi
authors.initials: R
authors.lastname: Kothary
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000071821:Dystonin; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008870:Microtubules / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D009475:Neurons, Afferent / Q000378:metabolism* / Q000648:ultrastructure; D015388:Organelles / Q000378:metabolism / Q000648:ultrastructure; D021381:Protein Transport / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C095667:Dst protein, mouse; D000071821:Dystonin; D009419:Nerve Tissue Proteins