Sheila A. Baker
Assistant ProfessorUniversity of Iowa
Biochemistry, 4-712 BSB
51 Newton Rd
Iowa City, IA
I use transgenic X. laevis as a model system to study protein trafficking in photoreceptors. 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. 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.