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Assistant Professor of BiochemistryAssistant Professor of
Ophthalmology and Visual Sciences
Primary Office: 4-712 BSBIowa City, IA 52242
Email: email@example.comWeb: Baker Laboratory
BS, Biology, University of Wisconsin, Stevens PointPhD, Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin
Post Doctorate, Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School
Department of Biochemistry PhDInterdisciplinary Graduate Program in Molecular and Cellular BiologyMedical Scientist Training Program
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. A third uniquely organized zone is the ribbon synapse where neurotransmitter is released.
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. This ultimately results in devastating blinding diseases such as retinitis pigmentosa or congenital stationary night blindness. 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 proteins of interest in the photoreceptors of living animals. The advantage is that the relatively large size of tadpole photoreceptors allows us to readily determine to which subcellular compartment that protein is trafficked. We also take advantage of genetically modified mouse strains to probe the consequences of altering photoreceptor organization in a retina more similar to the human retina. A few of the membrane proteins we are currently investigating include Na/K-ATPase, the ubiquitous sodium pump, HCN1, a cation channel in the inner segment essential for shaping the electrical output of the cell and Cav1.4, a voltage gated calcium channel needed for development of the synapse and neurotransmission.
Stephen A. Wynn Institute for Vision Research
TRIP8b is required for maximal expression of HCN1 in the mouse retina.
2014 January 7. 9(1):e850850.
Dysregulation of Cav 1.4 channels disrupts the maturation of photoreceptor synaptic ribbons in congenital stationary night blindness type 2.
2013 September 24. 7(6).
Cav1.4 IT mouse as model for vision impairment in human congenital stationary night blindness type 2.
2013 September 19. 7(6).
Protein sorting, targeting and trafficking in photoreceptor cells.
Progress in retinal and eye research.
A single valine residue plays an essential role in peripherin/rds targeting to photoreceptor outer segments.
Photoreceptor inner and outer segments.
Curr Top Membr.
Membrane attachment is key to protecting transducin GTPase-activating complex from intracellular proteolysis in photoreceptors.
The Journal of neuroscience : the official journal of the Society for Neuroscience.
2011 October. 31(41):14660-8.
Facilitative glucose transporter Glut1 is actively excluded from rod outer segments.
Journal of cell science.
2010 November. 123(21):3639-44.
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.
Protoreceptors and Intraflagellar Transport. Recent Advances in Human Biology.
Photoreceptor Cell Biology and Inherited Retinal Degenerations.
Date Last Modified: 10/09/2015 -
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