Ophthalmology And Visual Sciences

Sheila A. Baker, PhD

Portrait

Assistant Professor of Biochemistry
Assistant Professor of Ophthalmology and Visual Sciences

Contact Information

Primary Office: 4-712 BSB
Iowa City, IA 52242
Primary Office Phone: 319-353-4119

Email: sheila-baker@uiowa.edu
Web: Baker Laboratory

Education

BS, Biology, University of Wisconsin, Stevens Point
PhD, Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin

Post Doctoral, Harvard Medical School
Research Associate, Ophthalmology, Duke University Medical Center

Education/Training Program Affiliations

Biosciences Graduate Program
Department of Biochemistry PhD
Interdisciplinary Graduate Program in Molecular and Cellular Biology
Medical Scientist Training Program

Research Summary

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. 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. 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.

Center, Program and Institute Affiliations

Institute for Vision Research

Selected Publications

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Gospe S, Baker S, Arshavsky V.  Facilitative glucose transporter Glut1 is actively excluded from rod outer segments.  Journal of cell science.  2010 November. 123(21):3639-44.
[PubMed]

Bhowmick R, Li M, Sun J, Baker S, Insinna C, Besharse J.  Photoreceptor IFT complexes containing chaperones, guanylyl cyclase 1 and rhodopsin.  Traffic (Copenhagen, Denmark).  2009 June. 10(6):648-63.
[PubMed]

Kizhatil K, Baker S, Arshavsky V, Bennett V.  Ankyrin-G promotes cyclic nucleotide-gated channel transport to rod photoreceptor sensory cilia.  Science (New York, N.Y.).  2009 March. 323(5921):1614-7.
[PubMed]

Baker S, Haeri M, Yoo P, Gospe S, Skiba N, Knox B, Arshavsky V.  The outer segment serves as a default destination for the trafficking of membrane proteins in photoreceptors.  The Journal of cell biology.  2008 November. 183(3):485-98.
[PubMed]

Luby-Phelps K, Fogerty J, Baker S, Pazour G, Besharse J.  Spatial distribution of intraflagellar transport proteins in vertebrate photoreceptors.  Vision research.  2008 February. 48(3):413-23.
[PubMed]

Baker S, Martemyanov K, Shavkunov A, Arshavsky V.  Kinetic mechanism of RGS9-1 potentiation by R9AP.  Biochemistry.  2006 September. 45(35):10690-7.
[PubMed]

Baker S, Pazour G, Witman G, Besharse J.  Protoreceptors and Intraflagellar Transport. Recent Advances in Human Biology.  Photoreceptor Cell Biology and Inherited Retinal Degenerations.  2004. 10:109-132.

Baker S, Freeman K, Luby-Phelps K, Pazour G, Besharse J.  IFT20 links kinesin II with a mammalian intraflagellar transport complex that is conserved in motile flagella and sensory cilia.  The Journal of biological chemistry.  2003 September. 278(36):34211-8.
[PubMed]

Pazour G, Baker S, Deane J, Cole D, Dickert B, Rosenbaum J, Witman G, Besharse J.  The intraflagellar transport protein, IFT88, is essential for vertebrate photoreceptor assembly and maintenance.  The Journal of cell biology.  2002 April. 157(1):103-13.
[PubMed]

Date Last Modified: 03/20/2014 - 13:07:13