Participant: PROMISE AGEP Research Symposium
Institution: University of Maryland Baltimore (UMB)
Understanding Regulation of Intercellular Calcium
Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) regulates intracellular Ca2+ concentrations by clearing cytosolic Ca2+ into the lumen of the endoplasmic reticulum, and, in muscle, the sarcoplasmic reticulum (SR). Three major isoforms of SERCA include SERCA1, primarily expressed in skeletal muscle, SERCA2A, primarily expressed in cardiac muscle, and SERCA2B, which is ubiquitously expressed. SERCA1 is known to be inhibited by sarcolipin (SLN), a small transmembrane protein. My lab has recently shown that SERCA1 activity is also inhibited by small ankyrin 1 (sAnk1), a ~20kDa transmembrane protein that also binds to the cytoskeletal protein, obscurin. I have demonstrated SERCA1, SLN, and sAnk1 can form a three-way complex. SERCA2B is known to be expressed within the ER of glial cells and neurons, where it is found particularly in dendrites and spines. However, it is unknown if sAnk1 regulates SERCA2B in brain tissue. I am now determining if, like SERCA2B, SLN and sAnk1 are expressed in neurons, and if so, if they regulate the activity of SERCA2B in the same way that they affect SERCA1. These results have significant implications for the development of therapeutic approaches to treat a variety of diseases linked to calcium misregulation such as muscular dystrophies and neuropathies.
Amanda earned her Bachelor of Science degree in Biochemistry/Biophysics from Rensselaer Polytechnic Institute in 2012. From there she joined the doctoral program in neuroscience at the University of Maryland, Baltimore. She expects to graduate in winter of 2018. Her doctoral research is focused multiprotein complexes that regulate calcium reuptake into the sarcoendoplasmic reticulum in skeletal muscle and neurons. Amanda has had the opportunity to present her research at several conferences including three appearances at the international Society for Neuroscience conference.
In addition to obtaining her doctoral degree, Amanda served as president of the Neuroscience Outreach and Volunteer Association (NOVA). NOVA works with various programs and local Baltimore schools to teach young students about neuroscience and increase their enthusiasm for studying science. Amanda has increased NOVA’s membership, involvement in the community, and public relations.
GENERAL SUMMARY OF GRADUATE RESEARCH
My doctoral research focuses on the intercellular regulation of calcium through sarco(endo)plasmic reticulum Ca2+-ATPase1 (SERCA1). SERCA1 transports Ca2+ against its gradient into the SER after muscle contraction. SERCA is known to be regulated by sarcolipin (SLN) in fast twitch skeletal muscle and atrial cardiac muscle and phospholamban (PLN) in slow twitch muscle and ventricular cardiac muscle. Small Ankyrin 1 (sAnk1), a small transmembrane protein was recently shown to ablate SLN inhibition (Desmond et al., 2017).
SLN, PLN, and sAnk1 have all been shown to interact with SERCA through their transmembrane domain. The interaction of SERCA with SLN and PLN has been studied individually and together, but the effects of sAnk1 and its regulatory activity have only recently started to be addressed (Desmond et al., 2015, 2017). Studying the multi-protein complex of SERCA1, sAnk1, SLN, and/or PLN can help us better understand physiological SERCA regulation. This knowledge can lead to better treatment for diseases related to misregulation of calcium including muscular dystrophies.
Several neurodegenerative diseases are also associated with misregulation of calcium. The regulation of SERCA2B, the primary isoform found in neurons, is understudied. I propose that sAnk1 can regulate SERCA2B in neurons, possibly through a multi-protein complex with SLN.
SELECTED LIST OF PRESENTATIONS AND PUBLICATIONS
- Patrick F. Desmond, Amanda Labuza, Joaquin Muriel, Michele L. Markwardt, Allison E. Mancini, Mark A. Rizzo, Robert J. Bloch (2017) “Interactions between small ankyrin1 and sarcolipin coordinately regulate activity of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA1)”, Journal of Biological Chemistry.
- Amanda Labuza, Patrick F. Desmond, Joaquin Muriel, Michele L. Markwardt, Allison E. Mancini, Mark A. Rizzo, Robert J. Bloch (2017) “Comparison of small ankyrin 1 and sarcolipin regulation of SERCA1 in myocytes to SERCA2B in neurons”, Society for Neuroscience; Washington, DC
- Amanda Labuza, Quinton Banks, Kara Cover (2017) “NOVA: Providing graduate students with outreach opportunities to Baltimore”, Society for Neuroscience; Washington, DC
- Amanda Labuza, Patrick F. Desmond, Joaquin Muriel, Michele L. Markwardt, Allison E. Mancini, Mark A. Rizzo, Robert J. Bloch (2017) “Three-way Interaction of Sarco(endo)plasmic Reticulum Calcium-ATPase 1, Small Ankyrin 1, and Sarcolipin”, UMB Muscle and Membrane Retreat, Baltimore, MD
- Amanda Labuza, Patrick F. Desmond, Joaquin Muriel, Michele L. Markwardt, Allison E. Mancini, Mark A. Rizzo, Robert J. Bloch (2016) “Association of Small Ankyrin 1 with Sarcolipin”, Society for Neuroscience; San Diego, CA
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