Neurons are highly polarized cells that are specialized for information processing in the nervous system and depend upon microtubule (MT)- based transport systems for their assembly, maintenance and function. For example, chemosensory neurons in the nematode, Caenorhabditis elegans, are bipolar cells that use ciliated dendrites to detect chemicals in the environment (e.g. chemoattractants released by their bacterial food) and that transmit signals from their axons to coordinate the appropriate motile response (e.g. movement towards the source of the chemoattractant). We hypothesize that the formation and function of dendrites and sensory cilia on these chemosensory neurons depend upon MT-based intradendritic and intraciliary transport driven by two heteromeric kinesins, heterotrimeric kinesin-ll and dimeric Osm-3, whereas neurotransmission depends upon axonal transport driven, in part, by the monomeric kinesin, Unc-104. To test this hypothesis, the specific aims are: 1. To use EM and an in vivo transport assay to characterize the basic transport apparatus (i.e. motors, MT tracks and transport rafts/vesicles) operating in chemosensory neurons. 2. To dissect the functional relationships between the kinesin-Il and Osm-3 transport pathways in the formation and function of dendrites and sensory cilia. 3. To dissect the roles of Unc-104 in the binding and axonal transport of synaptic vesicles. 4. To study the relationship between intraciliary transport and chemosensory behavior of the adult C. elegans. Collectively, these studies will improve our understanding of the role of MT-based transport in the formation and function of neurons and in the control of the behavior of a primitive metazoan.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM050718-12
Application #
6916324
Study Section
Special Emphasis Panel (ZRG1-CDF-4 (02))
Program Officer
Rodewald, Richard D
Project Start
1994-05-01
Project End
2007-03-31
Budget Start
2005-07-01
Budget End
2007-03-31
Support Year
12
Fiscal Year
2005
Total Cost
$280,216
Indirect Cost
Name
University of California Davis
Department
Anatomy/Cell Biology
Type
Schools of Arts and Sciences
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Prevo, Bram; Scholey, Jonathan M; Peterman, Erwin J G (2017) Intraflagellar transport: mechanisms of motor action, cooperation, and cargo delivery. FEBS J 284:2905-2931
Prevo, Bram; Mangeol, Pierre; Oswald, Felix et al. (2015) Functional differentiation of cooperating kinesin-2 motors orchestrates cargo import and transport in C. elegans cilia. Nat Cell Biol 17:1536-45
Scholey, Jonathan M (2013) Kinesin-2: a family of heterotrimeric and homodimeric motors with diverse intracellular transport functions. Annu Rev Cell Dev Biol 29:443-69
Scholey, Jonathan M (2013) Compare and contrast the reaction coordinate diagrams for chemical reactions and cytoskeletal force generators. Mol Biol Cell 24:433-9
Brust-Mascher, Ingrid; Ou, Guangshuo; Scholey, Jonathan M (2013) Measuring rates of intraflagellar transport along Caenorhabditis elegans sensory cilia using fluorescence microscopy. Methods Enzymol 524:285-304
Scholey, Jonathan M (2012) Kinesin-2 motors transport IFT-particles, dyneins and tubulin subunits to the tips of Caenorhabditis elegans sensory cilia: relevance to vision research? Vision Res 75:44-52
Hao, Limin; Efimenko, Evgeni; Swoboda, Peter et al. (2011) The retrograde IFT machinery of C. elegans cilia: two IFT dynein complexes? PLoS One 6:e20995
Hao, Limin; Thein, Melanie; Brust-Mascher, Ingrid et al. (2011) Intraflagellar transport delivers tubulin isotypes to sensory cilium middle and distal segments. Nat Cell Biol 13:790-8
Pan, Xiaoyu; Acar, Seyda; Scholey, Jonathan M (2010) Torque generation by one of the motor subunits of heterotrimeric kinesin-2. Biochem Biophys Res Commun 401:53-7
Hao, Limin; Scholey, Jonathan M (2009) Intraflagellar transport at a glance. J Cell Sci 122:889-92

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