How is Motor-Driven Transport Regulated?
Background On Our Research

Microtubule motors are involved in many transport processes. The basic transport machinery is understood in great detail. As an example, look at the wealth of information available for the motor kinesin, compiled on the kinesin home page. However, it remains unclear how the activity of motors is integrated with the other processes that occur inside the cell: How are motors deployed in a regulated fashion?

We study this problem in Drosophila embryos because large-scale transport can easily be observed at the level of the whole embryo. This property allows us to use the power of Drosophila genetics to identify potential regulators of transport. We have recently performed a genetic screen for mutations that alter organelle transport and have found more than 25 candidates.

We can also follow directly the motion of individual organelles to probe the real-time behavior of the motors responsible for transport.  It is even possible to estimate how many motors are active per droplet by measuring the force powering droplet transport.  For this biophysical analysis, we collaborate with Dr. Steven Gross (University of California at Irvine).

The power of combining genetic and biophysical analysis has allowed us to propose several new concepts for motor regulation in vivo (coordination of opposite-polarity motors; a switching mechanism that terminates cargo motion before motor processivity becomes limiting), concepts that had not been anticipated from studies of motors in vitro. The principles discovered for droplet transport will likely be generally applicable because molecules important for droplet motion are also involved in other transport processes.


Current projects in the lab include:

• Molecular characterization of two new regulators of transport, Halo and OWS (One-Way Street)
• Determinants that control the specificity of organelle transport
• Genetic and biochemical identification of new molecules involved in droplet transport
• Employing these tools to understand other transport processes, such as RNA trafficking, axonal transport, and nuclear migration

S.P. Gross, Y. Guo, J.E. Martinez, M.A. Welte (2003).
"A Determinant for Directionality of Organelle Transport in Drosophila Embryos".
Curr. Biol. 13:1660-1668. Abstract

S. P. Gross, M. A Welte, S. M. Block, E. F. Wieschaus (2002).
"Coordination of opposite-polarity microtubule motors".
J. Cell Biol. 156:715-724. Abstract | More Info

S. P. Gross, M. A Welte, S. M. Block, E. F. Wieschaus (2000).
"Dynein-mediated cargo transport in vivo. A switch controls travel distance".
J. Cell Biol. 148:945-956. Abstract | More Info | Full text

M. A. Welte, S. P. Gross, M. Postner, S. M. Block, E. F. Wieschaus (1998).
" Developmental regulation of vesicle transport in Drosophila embryos: forces and kinetics".
Cell 92:547-557.  Abstract | More Info

Cohen, R.S. (2003). Halo: A Guiding Light for Transport. Curr. Biol. 13:R869-R870.

Maly, I.V. (2002). A stochastic model for patterning of the cytoplasm by the saltatory movement. J Theor Biol. 216:59-71.

Fischer, J.A. (2000). Molecular motors and developmental asymmetry. Curr Opin Genet Dev. 10:489-496.

Jäckle, H., and R. Jahn (1998). Vesicle transport: klarsicht clears up the matter. Curr. Biol. 8:R542-R544.