Department of Biochemistry
Iowa City, IA 52242-1109 USA
fax: (319) 335-9570
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Sheila Baker, PhD
Carver College of Medicine
University of Iowa
51 Newton Rd, 4-712 BSB
Iowa City, IA 52242
Phone: (319) 353-4119
Lab: (319) 335-6516
Fax: (319) 335-9570
Figure 1: Organization of the photoreceptor.
Cellular compartmentalization is a feature of all eukaryotic cells, and the vertebrate photoreceptor is one of the most elegant examples. Due to the polarized, layered structure of the photoreceptor, the major compartments are readily distinguished and include the outer segment, inner segment, nuclear layer and synaptic terminal. The plasma membrane of the cell is similarly compartmentalized and can be broadly divided into two regions, the outer segment plasma membrane and the inner segment plasma membrane – characterized by different protein compositions and separated by a diffusional barrier at the junction of these two compartments. This organization allows for the segregation of discrete functions and contributes to the photoreceptor’s exquisite ability to detect light and communicate that information to other neurons. For instance, the phototransduction cascade, one of the best studied G-protein signaling pathways, is confined to the membrane discs of the outer segment; while energy production, metabolism, lipid and protein synthesis are confined to the inner segment.
The goal of my lab is to uncover the cellular and molecular mechanisms that govern the sorting, trafficking, and delivery of membrane proteins from their site of synthesis in the inner segment to the various photoreceptor compartments. We believe this work will impact our understanding of health and disease because there are many examples of genetic mutations that prevent the trafficking of specific proteins or cause a breakdown in the overall compartmentalization of the photoreceptor, ultimately resulting in devastating blinding diseases such as retinitis pigmentosa. Understanding the patterns and molecular details of the various protein trafficking pathways utilized by this cell should aid our progress in developing therapies to save and restore vision.
Figure 2: Transgenic tadpole photoreceptors expressing fluorescent markers for the outer segment (green), endoplasmic reticulum (orange), and inner segment plasma membrane - synaptic terminal (red). Nuclei are labeled in blue.
One of the experimental systems utilized in my lab is the transgenic frog. This system allows us to rapidly express any protein of interest in the photoreceptors of living animals, and the relatively large size of tadpole photoreceptors allows us to readily determine to which compartment that protein is trafficked (Figure 2).
Currently, there are three major projects under investigation. In the first, we are investigating how the sodium pump, Na/K-ATPase, is selectively targeted to the photoreceptor inner segment plasma membrane. Second, we are unraveling the targeting signal that directs HCN1, a cation channel essential for shaping the electrical output of the cell, to the inner segment plasma membrane and synaptic terminal. Third, we are dissecting the trafficking pathway taken by synaptophysin, a marker for synaptic vesicles, as it moves through the secretory pathway and is incorporated into newly forming synaptic vesicles.
- Gospe SM, Baker SA and Arshavsky VY.(2010) Facilitative glucose transporter Glut1 is actively excluded from rod outer segments. Journal of Cell Science 123(21):3639-44. Download pdf reprint
- Kizhatil K, Baker SA, Arshavsky VY and Bennett V. (2009) Ankyrin-G promotes cyclic nucleotide-gated channel transport to rod photoreceptor sensory cilia.” Science, 323(5921): 1614-1617. Download pdf reprint
- Bhowmick R, Li M, Sun J, Baker SA, Insinna C and Besharse JC. (2009) Photoreceptor IFT complexes containing chaperones, Guanylyl Cyclase 1, and Rhodopsin. Traffic, 10(6): 648-663. Download pdf reprint
- Baker SA, Haeri M, Yoo P, Gospe SM, Skiba NP, Knox BE, and Arshavsky VY. (2008) The outer segment serves as a default destination for the trafficking of membrane proteins in photoreceptors. Journal of Cell Biology, 183(3): 485-498. Download pdf reprint
- Luby-Phelps K, Fogerty J, Baker SA, Pazour GJ, and Besharse JC. (2008) Spatial distribution of intraflagellar transport proteins in vertebrate photoreceptors. Vision Research, 48(3): 413-423. Download pdf reprint
- Baker SA, Martemyanov KA, Shavkunov AS and Arshavsky VA. (2006) Kinetic mechanism of RGS9-1 potentiation by R9AP. Biochemistry, 45(35): 10690-10697 Download pdf reprint
- Baker SA, Pazour GJ, Witman GB and Besharse JC. (2004) Photoreceptors and intraflagellar transport. Recent Advances in Human Biology; Photoreceptor Cell Biology and Inherited Retinal Degenerations, 10: 109-132. Edited by Williams DS.
- Baker SA, Freeman K, Luby-Phelps K, Pazour GJ and Besharse JC. (2003) IFT20 links Kinesin II with a mammalian intraflagellar transport complex that is conserved in motile flagella and sensory cilia. Journal of Biological Chemistry, 278(36): 34211-34218. Download to reprint
- Pazour GJ, Baker SA, Deane JA, Cole DG, Dickert BL, Rosenbaum JL, Witman GB and Besharse JC. (2002) The intraflagellar transport protein, IFT88, is essential for vertebrate photoreceptor assembly and maintenance. Journal of Cell Biology, 157(1): 103-113. Download to reprint
Ophthalmology & Visual Sciences
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