Molecular Cell & Developmental Biology
225 Sinsheimer Laboratories
Phone: 831.459.4986
Fax: 831.459.3139
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BILL SAXTON Professor of MCD Biology B.S., Microbiology, University of Minnesota Ph.D., Molecular, Cell and Developmental Biology, University of Colorado, Boulder SAXTON LAB

225 Sinsheimer Laboratories University of California Santa Cruz, CA 95064 phone 831.459.4914 fax 831.459.3139 saxton@biology.ucsc.edu office hours

Our group studies mechanisms that drive intracellular transport and cytoplasmic organization, using two invertebrate model systems: Drosophila and C. elegans.  We are currently addressing questions in three areas:  axonal organelle transport in Drosophila, which is critical for neuron function and viability, cytoplasmic movements in Drosophila oocytes, which ensure proper body axis patterning and embryonic development, and mitotic chromosome movements in C. elegans embryos, which are necessary for normal cell division.

Eukaryotes have evolved diverse arrays of proteins to accomplish their many intracellular transport processes.  Most transport mechanisms employ motor proteins that use ATP to move in one direction or the other along a polarized cytoskeletal filament.  Although the concept of motor-driven transport along a linear filament is simple, real transport mechanisms are surprisingly complex and not well understood.  Three large families of motor protein genes have been identified based on sequence similarities to myosin, dynein, or kinesin.  Proteins within each family have similar globular 'head', domains that couple ATP hydrolysis to a cycle of filament binding, conformational change, and filament release that can create force and stepwise movement.  Outside the head region, protein sequences are unrecognizably different.  Those 'stalk-tail' regions are thought to mediate cargo-linkage or other effector functions.  The transport of an organelle, RNA particle or other large cargoes to a particular destination in a cell can be influenced by a number of things, such as:  1) its ability to bind specific motors that have different transport capabilities,  2) regulation of when motor binding occurs,  3) regulation of motors' activities after they are bound, and  4) organization of the filament tracks that the motor walks on. 

Our model systems are highly relevant to human biology and health.  Our early studies of Drosophila motor mutants suggested that defects in microtubule motor driven fast transport contribute to human neurodegenerative diseases.  It has now been shown that mutations in genes for kinesin, dynein, and microtubule regulators can cause hereditary spastic paraplegia and other serious disorders.  Inhibition of kinesin-1 causes severe defects in body axis determination during oocyte development, and inhibition of mitotic motors and other proteins causes chromosome segregation defects in early C. elegans embryos, problems that in humans cause birth defects and cancer.  Thus, in-depth basic research on transport mechanisms in both model systems has had and will continue to have substantial impact on our understanding of the cellular mechanisms that underlie major human diseases.

Recent Publications

Serbus, L.R., B.J. Cha, W. Theurkauf, and W.M. Saxton.  2005.  Dynein and the actin cytoskeleton control kinesin-driven cytoplasmic streaming in Drosophila oocytes.  Development 132:3743-3752.

Hollenbeck, P.J. and W.M. Saxton.  2005.  The axonal transport of mitochondria.  J. Cell Sci. 18:5411-5419.

Horiuchi, D.,  R.V. Barkus, A.D. Pilling, A. Gassman, and W.M. Saxton.  2005.  APLIP1, a Kinesin-Binding JNK Scaffold Protein, Influences Bidirectional Transport of Vesicles and Retrograde Transport of Mitochondria in Drosophila Axons. Curr. Biol. 15:2137-2141.

Pilling, A., D Horiuchi, C.M. Lively and W. M. Saxton.  2006.  Kinesin-1 and dynein are the primary motors for fast transport of mitochondria in Drosophila motor axons.  Mol. Biol. Cell 17:2057-2068.

Saunders, A.M., J. Powers, S. Strome, and W.M. Saxton. 2007.  Anaphase spindle elongation:  A molecular motor acts as a brake.  Curr. Biol. 17:r453-455.

Horiuchi, D., C.A. Collins,, R.V. Barkus, P. Bhat, A. DiAntonio, and W.M. Saxton. 2007  Control of a kinesin-cargo linkage mechanism by JNK pathway kinases. Curr. Biol. (In Press).