Control of a Kinesin-Cargo Linkage Mechanism by JNK Pathway Kinases

Dai Horiuchi, Catherine A. Collins, Pavan Bhat, Rosemarie V. Barkus, Aaron DiAntonio, William M. Saxton

Research output: Contribution to journalArticle

115 Scopus citations

Abstract

Long-distance organelle transport toward axon terminals, critical for neuron development and function, is driven along microtubules by kinesins [1, 2]. The biophysics of force production by various kinesins is known in detail. However, the mechanisms of in vivo transport processes are poorly understood because little is known about how motor-cargo linkages are controlled. A c-Jun N-terminal kinase (JNK)-interacting protein (JIP1) has been identified previously as a linker between kinesin-1 and certain vesicle membrane proteins, such as Alzheimer's APP protein and a reelin receptor ApoER2 [3, 4]. JIPs are also known to be scaffolding proteins for JNK pathway kinases [5, 6]. Here, we report evidence that a Drosophila ubiquitin-specific hydrolase and a JNK signaling pathway that it modulates can regulate a JIP1-kinesin linkage. The JNK pathway includes a MAPKKK (Wallenda/DLK), a MAPKK (Hemipterous/MKK7), and the Drosophila JNK homolog Basket. Genetic tests indicate that those kinases are required for normal axonal transport. Biochemical tests show that activation of Wallenda (DLK) and Hemipterous (MKK7) disrupts binding between kinesin-1 and APLIP1, which is the Drosophila JIP1 homolog. This suggests a control mechanism in which an activated JNK pathway influences axonal transport by functioning as a kinesin-cargo dissociation factor.

Original languageEnglish
Pages (from-to)1313-1317
Number of pages5
JournalCurrent Biology
Volume17
Issue number15
DOIs
StatePublished - Aug 7 2007

Keywords

  • CELLBIO
  • SIGNALING

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    Horiuchi, D., Collins, C. A., Bhat, P., Barkus, R. V., DiAntonio, A., & Saxton, W. M. (2007). Control of a Kinesin-Cargo Linkage Mechanism by JNK Pathway Kinases. Current Biology, 17(15), 1313-1317. https://doi.org/10.1016/j.cub.2007.06.062