Nansi J. Colley

 

 

Molecular Genetics of Protein Trafficking in the Drosophila Visual System and Mechanisms of Neurodegeneration

E-mail: njcolley@wisc.edu

Research Strengths: Membrane Excitability and Synaptic Transmission, Molecular Neuroscience, Neurobiology of Disease

The research in my group explores the molecular genetic basis of signal transduction in the photoreceptor cells of Drosophila melanogaster. Our goal is to identify the molecular components underlying protein targeting and transport as well as calcium modulation. Phototransduction in Drosophila utilizes a G protein-coupled phospholipase-C-mediated signaling cascade that is regulated by calcium. Light stimulation of the receptor, rhodopsin, activates a heterotrimeric G protein of the Gq family which activates a phospholipase C encoded by the norpA gene. We are focused on the precise targeting and transport mechanisms that assemble the constituents of phototransduction. Drosophila photoreceptors contain a photosensitive organelle called the rhabdomere. Rhabdomeres are functionally equivalent to the vertebrate photoreceptor outer segments and contain the rhodopsin photopigments and the other components of the phototransduction cascade. During biosynthesis, the members of phototransduction are specifically targeted and transported to the rhabdomeres. Drosophila is an ideal model system for the study of the assembly of G protein-coupled signaling cascades. Our studies in the fruit fly make use of powerful molecular genetic techniques to identify novel transport and transduction molecules, and we are able to examine the function of these molecules in vivo. The results obtained from our studies offer insights for the molecular basis of sensory reception as well as understanding abnormalities and disease in the human nervous system.

Website:

http://www.genetics.wisc.edu/faculty/colley.html

Selected Publications:

• Rosenbaum, E. E., R. C. Hardie, and N. J. Colley. 2006. Calnexin is essential for rhodopsin maturation, Ca2+ regulation and photoreceptor cell survival. Neuron. 49: 229-241. [PDF]
• LaLonde, M. M., H. Janssens, N. J. Colley, W. Stark, and M. A. Frohman. 2005. Regulation of phototransduction responsiveness and retinal degeneration by a phospholipase D-generated signaling lipid. J. Cell Biol. 169: 471-479. [PDF]
• Winkfein, R. J., B. Pearson, R. Ward, R. Szerencsei, N. J. Colley, and P. P. M. Schnetkamp. 2004. Molecular characterization, functional expression and tissue distribution of a second NCKX Na+/Ca2+-K+ exchanger from Drosophila. Cell Calcium. 36: 147-155. [PDF]
• Webel, R., K. Haug-Collet, B. Pearson, R.T. Szerencsei, R.J. Winkfein, P.P.M. Schnetkamp, and N. J. Colley. 2002. Potassium-dependent sodium-calcium exchange through the eye of the fly. Ann. N.Y. Acad. Sci. 976: 1-15. [PDF]
• Mollereau, B., M. Dominguez, R. Webel, N.J. Colley, J.F. deCelis, and C. Desplan. 2001. Two-step process for photoreceptor formation in Drosophila. Nature 412: 911-913. [PDF]
• Colley, N.J. 2000. Cell biology. Actin' up with Rac1. Science 290: 1902-1903. [PDF]
• Padinjat, R., N.J. Colley, R. Webel, T. James, G. Hasan, Z. Selinger, and R.C. Hardie. 2000. Normal phototransduction in Drosophila photoreceptors lacking an InsP3 receptor gene. Mol. Cell. Neursci. 15: 429-445.