Jim Wilhelm
Assistant Professor of Biology, UCSD

e-mail: jwilhelm@ucsd.edu
Lab Homepage:

   While a great deal is known about how proteins are sorted to various membrane bound compartments, very little is known about how proteins are sorted to particular domains within the cytoplasm.  One mechanism for localizing cytoplasmic proteins is to transport the mRNA encoding the protein to the desired location, so that the synthesis of the protein is spatially restricted to particular cytoplasmic regions.  Establishment of these domains is further enhanced by a translational control mechanism that ensures that only the properly targeted messages are translated.  This sorting mechanism has been implicated in processes as diverse as stem cell differentiation, regulating synaptic strength in neurons and embryonic pattern – underscoring the importance of understanding mRNA localization for medicine, neuroscience, and developmental biology.  While the importance of this method of sorting cytoplasmic proteins is clear, it is unclear how localized messages are targeted to different domains or how many cellular or developmental processes utilize mRNA localization.  My lab utilizes a combination of genetics, biochemistry, and microscopy to study mRNA localization events in Drosophila melanogaster.

An unexpected link between ER exit and mRNA trafficking

   While most of the focus in the field of mRNA localization and translational control has been on regulation of key developmental molecules, it has been unclear how broad a role these two regulatory mechanisms play in basic cellular processes.  Trailer hitch (tral) was identified as part of a RNA localization complex, however, genetic analysis revealed that tral is required for efficient secretion. We were able to reconcile these observations when we discovered that the Tral complex is present on subdomains of the endoplasmic reticulum (ER) that border ER exit sites - the sites where ER to Golgi trafficking takes place.  Furthermore, tral is required for normal ER exit site formation and is associated with the mRNAs for ER exit site components.  These findings have raised exciting new possibilities for how the mRNA localization machinery could interface with the classical secretory pathway to promote efficient protein trafficking in the cell (Wilhelm, et al., 2005). 

We are currently characterizing how mRNAs might be sorted to the ER as well as other components of the complex with the ultimate goal of identifying novel roles for mRNA localization in regulating basic cellular functions.

   Wilhelm, J. E.*, Buszczak, M., and Sayles, S. (2005) Efficient protein trafficking requires Trailer Hitch, a component of a ribonucleoprotein complex localized to the ER in Drosophila. Dev. Cell 9(5):675-85.

   Wilhelm,J.E.*, Hilton,M., Amos,Q.  and Henzel,W.J. (2003) Cup is an eIF4E binding protein required for both the translational repression of oskar and the recruitment of Barentsz.  J. Cell Biol. 163:1197-204.

   Mansfield, J.H., Wilhelm, J.E. and Hazelrigg, T. (2002) Ypsilon Schachtel, a Drosophila Y-box Protein, Acts Antagonistically to Orb in the oskar mRNA Localization and Translation Pathway, Development. 129: 197-209.

   Wilhelm, J.E., Vale, R.D., Hegde, R.S.  (2000) Coordinate Control of Translation and Localization of Vg1 mRNA in Xenopus Oocytes, P.N.A.S. 97: 13132-13137.

   Takizawa, P.A., DeRisi, J.L., Wilhelm, J.E., Vale, R.D. (2000) mRNA Localization and a Septin-Based Diffusion  Barrier Create an Asymmetric Distribution of a Yeast Plasma Membrane Protein, Science. 290:341-344.

   Wilhelm, J.E., Mansfield, J., Hom-Booher, N., Wang, S., Turck, C.W., Hazelrigg, T., Vale, R.D.  (2000)  Isolation of a Ribonucleoprotein Complex Involved in mRNA Localization in Drosophila Oocytes, J. Cell Biol. 148: 427-439.

Reviews

   Wilhelm, J.E. and Vale, R.D.  (1993) RNA on the Move: The mRNA Localization Pathway.  J. Cell Biol. 123: 269-274.

   Wilhelm,  J.E.*, Smibert, C.A.(2005) Mechanisms of translational regulation in Drosophila. Biol Cell. 97(4):235-52.

* Indicates papers in which Dr. Wilhelm is the corresponding author

Jim Wilhelm received his Ph.D. in Cell Biology from University of California, San Francisco. He then took a Staff Associate (independent postdoctoral position) in the Department of Embryology, Carnegie Institution of Washington where he received funding from the Life Sciences Research Foundation as a Howard Hughes Medical Institute Fellow.