Identification of an axonal kinesin-3 motor for fast anterograde vesicle transport that facilitates retrograde transport of neuropeptides.
A screen for genes required in Drosophila eye development identified an UNC-104/Kif1 related kinesin-3 microtubule motor. Analysis of mutants suggested that Drosophila Unc-104 has neuronal functions that are distinct from those of the classic anterograde axonal motor, kinesin-1. In particular, unc-104 mutations did not cause the distal paralysis and focal axonal swellings characteristic of kinesin-1 (Khc) mutations. However, like Khc mutations, unc-104 mutations caused motoneuron terminal atrophy. The distributions and transport behaviors of green fluorescent protein-tagged organelles in motor axons indicate that Unc-104 is a major contributor to the anterograde fast transport of neuropeptide-filled vesicles, that it also contributes to anterograde transport of synaptotagmin-bearing vesicles, and that it contributes little or nothing to anterograde transport of mitochondria, which are transported primarily by Khc. Remarkably, unc-104 mutations inhibited retrograde runs by neurosecretory vesicles but not by the other two organelles. This suggests that Unc-104, a member of an anterograde kinesin subfamily, contributes to an organelle-specific dynein-driven retrograde transport mechanism.
Barkus
Rosemarie V
RV
Department of Biology, Indiana University, Bloomington, IN 47405-3700, USA.
Klyachko
Olga
O
Horiuchi
Dai
D
Dickson
Barry J
BJ
Saxton
William M
WM
D000818:Animals; D001369:Axons / Q000378:metabolism*; D001692:Biological Transport; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009479:Neuropeptides / Q000378:metabolism*; D015388:Organelles / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism*
C069672:Csp protein, Drosophila; D029721:Drosophila Proteins; D009479:Neuropeptides; D049452:Green Fluorescent Proteins; C587248:Unc-104 protein, Drosophila; D016547:Kinesins