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Teaching: General Biology I; Principles in Biology; Current Applications (DNA Science) Research: Cell Biology and Biochemistry My research interests lie within the field of retina cell biology. For the past several years, I have been studying protein interactions on and between glial cells and photoreceptor neurons. Photoreceptor cells are the neurons in the retina that are responsible for vision. There are two types of photoreceptor cells, called rods and cones. Rods are used for seeing in times of low light (black and white), whereas cones are used for day-time and color vision. There is one type of glial cell in the retina, called Müller cells. It is thought that Müller cells are support cells for the photoreceptors. They provide the rods and cones with molecules necessary for biological processes, such as cellular respiration. Specifically, I study products of the Basigin gene and also a group of transport proteins called monocarboxylate transporters (MCTs). The Basigin gene codes for two products, which result from variation in RNA splicing. The smaller gene product, named Basigin, is a glycoprotein of ~45 kDa that is found on the plasma membrane of epithelial cells throughout the body, as well as Müller cells and blood vessel endothelial cells in the retina, and the retinal pigmented epithelium (cell layer directly beneath the retina). The larger gene product, named Basigin-2, is a glycoprotein of ~50 kDa that is found only on photoreceptor cells (inner segments) of the retina. The two gene products are identical in amino acid sequence, with the exception of an additional 116 amino acids near the amino terminus of Basigin-2. Both are immunoglobulin-like in structure. Basigin has two immunoglobulin domains, whereas Basigin-2 has three domains (the extra 116 amino acids account for this additional domain). Although biological functions for Basigin and Basigin-2 have yet to be determined, a strain of mouse that lacks both gene products (Basigin null mouse) is blind from the time of eye opening. MCT proteins have ten to twelve transmembrane domains and function to transport monocarboxylates, such as pyruvate and lactate. There are nine different MCTs, however, only four of these are found in the eye (MCT1, MCT2, MCT3, and MCT4). MCT1 is expressed by Müller cells, photoreceptor cells (inner segments), the retinal pigmented epithelium, and blood vessel endothelial cells in the eye. MCT2 and MCT4 are found in the neural retina, and MCT3 is expressed by the retinal pigmented epithelium. It is thought that MCTs on Müller cells transport lactate out of the cell and other MCTs on photoreceptor cells take up the lactate, which is used for cellular respiration in those cells. Several recent studies indicate that Basigin interacts with MCT1. In the Basigin null mouse, MCT1 is not found on the cell surface, but rather in intracellular vesicles. We propose that a lactate shuttle complex exists within the retina and is necessary for photoreceptor cell function. We hypothesize that the shuttle complex is composed of Basigin-MCT1 on Müller cells and Basigin2-MCT1 on photoreceptor cells, and that the two cell types are bound via the extracellular domains of the Basigin gene products. We also hypothesize that this shuttle complex cannot form in the Basigin null mouse; the photoreceptor cells do not receive lactate from the Müller cells; and therefore the photoreceptor cells do not function. A current research project in my laboratory is aimed at studying the lactate shuttle complex. Specifically, we are mapping the amino acids on the Basigin and the MCT1 polypeptides that interact with each other. We plan to expand these studies to the other MCT proteins in the retina as well. We are also testing whether the extracellular domains of Basigin and Basigin-2 interact. Another of my research interests is regulation of gene expression. As I mentioned above, there are two products coded by the Basigin gene. The splice variation, which produces two Basigin gene products, is most likely cell-specific, as Basigin-2 is only expressed in photoreceptor cells. I plan to study how this splice variation occurs by investigating the transcription factor and splice factor binding sites within the Basigin gene. Recent Publications: Ochrietor, J. D. and P. J. Linser. 2004. 5A11/Basigin gene products are necessary for proper maturation and function of the retina. Dev. Neurosci. 26: 380-387. Clamp, M. C., J. D. Ochrietor, T. P. Moroz, and P. J. Linser. 2004. Developmental expression of 5A11/Basigin family members in the mouse retina. Exp. Eye Res. 78: 777-789. Ochrietor, J. D., T. P. Moroz, L. van Ekeris, M. F. Clamp, S. C. Jefferson, A. C. V. deCarvalho, J. M. Fadool, G. Wistow, T. Muramatsu, and P. J. Linser. 2003. Retina-specific expression of 5A11/Basigin-2, a member of the immunoglobulin gene superfamily. Invest. Ophthal. Vis. Sci. 44: 4086-4096. Philp, N. J., J. D. Ochrietor, C. Rudoy, T. Muramatsu, and P. J. Linser. 2003. Loss of MCT1, MCT3 and MCT4 expression in the retinal pigmented epithelium and neural retina of the 5A11/Basigin null mouse. Invest. Ophthal. Vis. Sci. 44: 1305-1311. Ochrietor, J. D., T. P. Moroz, M. F. Clamp, A. M. Timmers, and P. J. Linser. 2002. Inactivation of the Basigin gene impairs normal retinal development and maturation. Vis. Res. 42: 447-453. Ochrietor, J. D., T. Moroz, K. Kadamatsu, T. Muramatsu, and P. J. Linser. 2001. Retinal degeneration following failed photoreceptor maturation in 5A11/Basigin null mice. Exp. Eye Res. 72: 467-77. |
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