Role of Neurogranin In The Regulation of Calcium Binding to Calmodulin

<p><strong>Role of Neurogranin in the regulation of calcium binding to Calmodulin</strong></p> <p><strong></strong>Anuja Chandrasekar, B.S</p> <p>Advisor: M. Neal Waxham, Ph.D</p> <p>The overall goal of my project was to gain a quantitative understanding of how the interaction between two proteins neurogranin (RC3) and calmodulin (CaM) alters a fundamental property of CaM. CaM, has been extensively studied for more than four decades due to its seminal role in almost all biological functions as a calcium signal transducer. Calcium signals in cardiac and neuronal cells are exquisitely precise and enable activation of some processes while down-regulating others. CaM, with its four calcium binding sites, serves as a central component of calcium signaling in these cells. It is aided in this role as a regulatory hub that differentially activates targets in response to a calcium flux by proteins that alter its calcium binding properties.</p> <p>Neurogranin, also known as RC3, is a member of a family of small neuronal IQ (SNIQ) domain proteins that was originally thought to play a ‘capacitive’ role by sequestering CaM until a calcium influx of sufficient intensity arrived. However, based on earlier work in our lab on neurogranin, we believe that this protein plays a more nuanced role in neurons than simply acting as a CaM buffer. We believe that neurogranin is one of the proteins which, by altering the kinetics of calcium binding allow CaM to decode a variety of signals with fine precision. To quantify the interaction between CaM, neurogranin and calcium, I used biophysical techniques and computational simulations. From my results, I conclude that neurogranin finely regulates the proportion of calcium-saturated CaM and thereby directs CaM’s target specificity.</p>

Name thesis:degree_name

Masters of Science (MS)

Level thesis:degree_level

Thesis (MS)

Year dc:date.available

2013

Author dc:creator

• Chandrasekar, Anuja

Contributors dc:contributor

• M.Neal Waxham
• Ruth Heidelberger
• Harel Z Shouval

• Calmodulin
• Neurogranin
• Calcium
• Isothermal Titration Calorimetry
• fluorimetry
• ODE simulation model
• Computational Neuroscience
• Medicine and Health Sciences
• Molecular and Cellular Neuroscience

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/373

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1407