title: Distinct intracellular vesicle transport mechanisms are selectively modified by spastin and spastin mutations.
abstract: Spastin is a microtubule severing ATPase that regulates intracellular and axonal transport of vesicles. Intracellular vesicle trafficking was analyzed in differentiated SH-SY5Y-neuroblastoma cells, transfected with spastin wild-type and three spastin mutations (ΔN, K388R, S44L) to investigate spastin-mediated effects on the velocity of vesicles, stained with LysoTracker Red®. The vesicle velocity varied considerably between mutations and detailed analysis revealed up to five distinct velocity classes. Microtubule severing by overexpressed wild-type spastin caused reduced vesicle velocity. S44L and ΔN mutations, which were functionally impaired, showed similar velocities as control cells. K388R-transfected cells exhibited an intermediate velocity profile. The results support the idea that spastin mutations not only alter axonal transport, but in addition regulate intracellular trafficking in the cell soma as well.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital of Erlangen, Erlangen, Germany.
authors.forename: Julia C
authors.initials: JC
authors.lastname: Fuerst
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Henkel
authors.forename: Armin
authors.initials: A
authors.lastname: Stroebel
authors.forename: Oliver
authors.initials: O
authors.lastname: Welzel
authors.forename: Teja W
authors.initials: TW
authors.lastname: Groemer
authors.forename: Johannes
authors.initials: J
authors.lastname: Kornhuber
authors.forename: Dominikus
authors.initials: D
authors.lastname: Bönsch
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D001370:Axonal Transport / Q000502:physiology*; D001692:Biological Transport / Q000502:physiology; D045744:Cell Line, Tumor; D022162:Cytoplasmic Vesicles / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D009154:Mutation; D000074181:Spastin
chemical_list: D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human