title: Neuropathogenic forms of huntingtin and androgen receptor inhibit fast axonal transport.
abstract: Huntington's and Kennedy's disease are autosomal dominant neurodegenerative diseases caused by pathogenic expansion of polyglutamine tracts. Expansion of glutamine repeats must in some way confer a gain of pathological function that disrupts an essential cellular process and leads to loss of affected neurons. Association of huntingtin with vesicular structures raised the possibility that axonal transport might be altered. Here we show that polypeptides containing expanded polyglutamine tracts, but not normal N-terminal huntingtin or androgen receptor, directly inhibit both fast axonal transport in isolated axoplasm and elongation of neuritic processes in intact cells. Effects were greater with truncated polypeptides and occurred without detectable morphological aggregates.
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Györgyi
authors.initials: G
authors.lastname: Szebenyi
authors.forename: Gerardo A
authors.initials: GA
authors.lastname: Morfini
authors.forename: Alyssa
authors.initials: A
authors.lastname: Babcock
authors.forename: Milena
authors.initials: M
authors.lastname: Gould
authors.forename: Kimberly
authors.initials: K
authors.lastname: Selkoe
authors.forename: David L
authors.initials: DL
authors.lastname: Stenoien
authors.forename: Maureen
authors.initials: M
authors.lastname: Young
authors.forename: Pieter W
authors.initials: PW
authors.lastname: Faber
authors.forename: Marcy E
authors.initials: ME
authors.lastname: MacDonald
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McPhaul
authors.forename: Scott T
authors.initials: ST
authors.lastname: Brady
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D048429:Cell Size / Q000502:physiology; D049832:Decapodiformes; D006801:Humans; D000071058:Huntingtin Protein; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D009433:Neural Inhibition / Q000502:physiology; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D010455:Peptides / Q000737:chemistry / Q000235:genetics; D011944:Receptors, Androgen / Q000737:chemistry / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; D011944:Receptors, Androgen; C097188:polyglutamine