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Show SCHOOL OF MEDICINE AND HEALTH SCIENCES NDERGRADUATE RESEARCH ABSTRACTS ROLE OF STIM1 AND STIM2 IN NEUROTRANSMISSION BETWEEN PHOTOCEPTOR CELLS AND SECONDARY NEURONS OF THE RETINA Trevor Gulbrandsen (Peter Barabas, David Krizaj) Department of Ophthalmology and Visual Sciences University of Utah The calcium ion (Ca2+) is one of the most important and versatile intracellular messengers. It affects metabolism, cell cycle and signaling within cells (integrating processes across different cellular compartments) and between cells. Release of Ca2+ from endoplasmic reticulum (ER) stores into the cytoplasm is used as a signal and is crucial for many temporally controlled processes like muscle contraction and neuronal signaling. STromal-lnteracting Molecule 1 (STIM1) and/or STIM2 are activated when the concentration of Ca2+ ([Ca2+]) drops within the ER stores due to release of Ca2+. These ER membrane proteins then translocate within the ER membrane to domains that come in close contact with the plasma membrane and activate the diverse family of store-operated Ca2+-channels. These channels let Ca2+from the extracellular space into the cytoplasm increasing cytoplasmic [Ca2+] and allowing replenishment of the ER stores. (Hewavitharana et al., 2007, Cell Calcium. 42:173-182; Putney 2011,Neurochem Res. 36:1157-1165). It has recently been shown (Cadetti et al., 2006, Eur J Neurosci. 23:2983-2990; Babai et al., 2010, Neuroscience. 165:1447-1456) that Ca2+ released from the ER stores in photoreceptor cell synapses can affect neurotransmitter release. Based on this finding, w e hypothesize that upon ER store usage, STIM1 and/or STIM2-mediated opening of store-operated Ca2+ channels may also affect neurotransmission between photoreceptor cells and postsynaptic secondary neurons. To examine this hypothesis w e tested the visual acuity of mouse strains with Stiml or Stim2 or both genes knocked out specifically in either rod or cone photoreceptor cells. W e tested specifically for rods and cones by conducting these experiments in darkness (scotopic, testing rod vision) using infrared illumination or normal lighting (photopic, testing cone vision) conditions. The visual acuity results (using Optomotor reflex-based test) provide strong evidence that STIM1 but not STIM2 play an important role in the neurotransmission between photoreceptor cells and secondary neurons of the retina. By showing that STIM1 affects the flow of visual information and vision itself, w e uncovered a new modulatory mechanism of signal transduction in the retina. David Krizaj 119 |
