title: APLIP1, a kinesin binding JIP-1/JNK scaffold protein, influences the axonal transport of both vesicles and mitochondria in Drosophila.
abstract: In a genetic screen for Kinesin heavy chain (Khc)-interacting proteins, we identified APLIP1, a neuronally expressed Drosophila homolog of JIP-1, a JNK scaffolding protein . JIP-1 and its homologs have been proposed to act as physical linkers between kinesin-1, which is a plus-end-directed microtubule motor, and certain anterograde vesicles in the axons of cultured neurons . Mutation of Aplip1 caused larval paralysis, axonal swellings, and reduced levels of both anterograde and retrograde vesicle transport, similar to the effects of kinesin-1 inhibition. In contrast, Aplip1 mutation caused a decrease only in retrograde transport of mitochondria, suggesting inhibition of the minus-end microtubule motor cytoplasmic dynein . Consistent with dynein defects, combining heterozygous mutations in Aplip1 and Dynein heavy chain (Dhc64C) generated synthetic axonal transport phenotypes. Thus, APLIP1 may be an important part of motor-cargo linkage complexes for both kinesin-1 and dynein. However, it is also worth considering that APLIP1 and its associated JNK signaling proteins could serve as an important signaling module for regulating transport by the two opposing motors.
authors.affiliation: Department of Biology, Indiana University, Bloomington, Indiana 47405, USA.
authors.forename: Dai
authors.initials: D
authors.lastname: Horiuchi
authors.forename: Rosemarie V
authors.initials: RV
authors.lastname: Barkus
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Pilling
authors.forename: Andrew
authors.initials: A
authors.lastname: Gassman
authors.forename: William M
authors.initials: WM
authors.lastname: Saxton
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D002874:Chromosome Mapping; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000502:physiology*; D004398:Dyneins / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism; D007814:Larva / Q000502:physiology; D008870:Microtubules / Q000378:metabolism; D008928:Mitochondria / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D017422:Sequence Analysis, DNA; D022161:Transport Vesicles / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D029721:Drosophila Proteins; D004398:Dyneins; D016547:Kinesins