title: Huntingtin differentially regulates the axonal transport of a sub-set of Rab-containing vesicles in vivo.
abstract: Loss of huntingtin (HTT), the Huntington's disease (HD) protein, was previously shown to cause axonal transport defects. Within axons, HTT can associate with kinesin-1 and dynein motors either directly or via accessory proteins for bi-directional movement. However, the composition of the vesicle-motor complex that contains HTT during axonal transport is unknown. Here we analyze the in vivo movement of 16 Rab GTPases within Drosophila larval axons and show that HTT differentially influences the movement of a particular sub-set of these Rab-containing vesicles. While reduction of HTT perturbed the bi-directional motility of Rab3 and Rab19-containing vesicles, only the retrograde motility of Rab7-containing vesicles was disrupted with reduction of HTT. Interestingly, reduction of HTT stimulated the anterograde motility of Rab2-containing vesicles. Simultaneous dual-view imaging revealed that HTT and Rab2, 7 or 19 move together during axonal transport. Collectively, our findings indicate that HTT likely influences the motility of different Rab-containing vesicles and Rab-mediated functions. These findings have important implications for our understanding of the complex role HTT plays within neurons normally, which when disrupted may lead to neuronal death and disease.
authors.affiliation: Department of Biological Sciences, The State University of New York at Buffalo, Buffalo, NY 14260, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: White
authors.affiliation: Department of Biological Sciences, The State University of New York at Buffalo, Buffalo, NY 14260, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Anderson
authors.affiliation: Department of Biological Sciences, The State University of New York at Buffalo, Buffalo, NY 14260, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Zimmerman
authors.affiliation: Department of Biological Sciences, The State University of New York at Buffalo, Buffalo, NY 14260, USA.
authors.forename: Kan Hong
authors.initials: KH
authors.lastname: Zheng
authors.affiliation: Department of Biological Sciences, The State University of New York at Buffalo, Buffalo, NY 14260, USA.
authors.forename: Roza
authors.initials: R
authors.lastname: Rouhani
authors.affiliation: Department of Biological Sciences, The State University of New York at Buffalo, Buffalo, NY 14260, USA sg99@buffalo.edu.
authors.forename: Shermali
authors.initials: S
authors.lastname: Gunawardena
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000235:genetics / Q000502:physiology*; D004330:Drosophila; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D020693:rab2 GTP-Binding Protein / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
chemical_list: D009419:Nerve Tissue Proteins; D000090802:rab7 GTP-Binding Proteins; D020691:rab GTP-Binding Proteins; D020693:rab2 GTP-Binding Protein