title: Kinesin-1 tail autoregulation and microtubule-binding regions function in saltatory transport but not ooplasmic streaming.
abstract: The N-terminal head domain of kinesin heavy chain (Khc) is well known for generating force for transport along microtubules in cytoplasmic organization processes during metazoan development, but the functions of the C-terminal tail are not clear. To address this, we studied the effects of tail mutations on mitochondria transport, determinant mRNA localization and cytoplasmic streaming in Drosophila. Our results show that two biochemically defined elements of the tail - the ATP-independent microtubule-binding sequence and the IAK autoinhibitory motif - are essential for development and viability. Both elements have positive functions in the axonal transport of mitochondria and determinant mRNA localization in oocytes, processes that are accomplished by biased saltatory movement of individual cargoes. Surprisingly, there were no indications that the IAK autoinhibitory motif acts as a general downregulator of Kinesin-1 in those processes. Time-lapse imaging indicated that neither tail region is needed for fast cytoplasmic streaming in oocytes, which is a non-saltatory bulk transport process driven solely by Kinesin-1. Thus, the Khc tail is not constitutively required for Kinesin-1 activation, force transduction or linkage to cargo. It might instead be crucial for more subtle elements of motor control and coordination in the stop-and-go movements of biased saltatory transport.
authors.affiliation: Department of Biology, Indiana University, Bloomington, IN 47405, USA.
authors.forename: Pangkong
authors.initials: P
authors.lastname: Moua
authors.forename: Donna
authors.initials: D
authors.lastname: Fullerton
authors.forename: Laura R
authors.initials: LR
authors.lastname: Serbus
authors.forename: Rahul
authors.initials: R
authors.lastname: Warrior
authors.forename: William M
authors.initials: WM
authors.lastname: Saxton
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001665:Binding Sites / Q000502:physiology; D001692:Biological Transport / Q000235:genetics / Q000502:physiology; D003595:Cytoplasmic Streaming / Q000235:genetics* / Q000502:physiology; D004330:Drosophila / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D025461:Feedback, Physiological / Q000502:physiology; D005260:Female; D016547:Kinesins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D008870:Microtubules / Q000378:metabolism*; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D054730:Protein Interaction Domains and Motifs / Q000235:genetics / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D008869:Microtubule-Associated Proteins; C515209:Khc protein, Drosophila; D016547:Kinesins