Calcium: More Than Just Bones and Teeth
Dr. David Yule
Louis C. Lasagna Professorship in Experimental Therapeutics
Professor of Pharmacology and Physiology
University of Rochester
The majority of calcium in the human body is stored as salts in bones and teeth and plays a purely structural role. A small percentage (less than 0.1%) of calcium is “free” inside cells and is present in its ionic form. This calcium (Ca2+) is dynamically regulated, such that neurotransmitters and hormones control the level of the ion on a moment-by-moment time scale. In turn, Ca2+ regulates diverse cellular processes including muscle contraction, gene transcription, secretion, learning and memory, cellular bioenergetics and cell fate. Dysregulation of this signaling pathway is increasingly implicated in human disease, including heart disease, spinocerebellar ataxia, Alzheimer’s and Huntington’s disease. A prominent mechanism utilized to increase Ca2+ following stimulation by hormones and neurotransmitters is through the receptor-activated, G-protein-coupled formation of the second messenger inositol 1,4,5-trisphosphate. This molecule binds to inositol 1,4,5-trisphosphate receptors (IP3R) which are ubiquitous, intracellular Ca2+ channels expressed predominantly in endoplasmic reticulum (ER) membranes. Activation of IP3R results in release of Ca2+ from the ER into the cytoplasm. IP3R can encode Ca2+ changes with distinct spatial and temporal characteristics and these signals subsequently play essential roles in precisely controlling biological processes with specificity and fidelity. The versatility of these signals is a consequence, in large part, of the regulation of IP3R activity at multiple levels. First, there are three isoforms of IP3R, termed the R1, R2 and R3, encoded by three different genes. IP3R can either form homo- or hetero-tetrameric channels. The composition of the assembled tetramer either dictates or contributes to the channel activity. Further, binding of numerous molecules or post-translational modification can regulate IP3R properties including the biophysical characteristics of activity. In the presentation, I will detail recent work by graduate students in my lab regarding how subtype-specific regulation of IP3R contributes to the generation of intracellular Ca2+ signals with distinct properties and how these signals control cell function.
Beginners, undergraduates, graduates, experts. Those with interest in the topic.
When and Where
1:00 PM-1:50 PM
Thomas Gosnell Hall
Open to the Public