Research Interests:

Many cellular functions are directly or indirectly regulated by free cytosolic calcium concentration. Thus, calcium levels must be tightly regulated in time, space and amount. Two important paths for increasing cytosolic calcium levels are through voltage-gated calcium channels in the plasma membrane, and ryanodine receptors in the sarcoplasmic or endoplasmic reticular membranes. Many studies have shown that alterations in these calcium channels can produce profound effects on cellular function and are associated with many human diseases. My research focuses on acquiring a better understanding of calcium channel function and protein interactions involved in calcium signaling in muscle and neurons.

In skeletal muscle, bi-directional signaling occurs between the voltage-gated calcium channels (DHPRs) and calcium release channels (RyRs). My research focuses on study of the protein-protein interactions involved in this signaling. This research utilizes two general approaches: functional studies to probe dynamic functional interactions required to trigger RyR1-mediated calcium release, and structural studies defining the spatial inter-relationship between DHPRs, RyRs and other proteins within plasma membrane-SR junctions.

In neurons, calcium influx and release from internal stores has been shown to play important role in many functions, such as neurite outgrowth, neuronal excitability, neurotransmitter release, synaptic efficacy, and gene transcription. Cerebellar Purkinje cells are remarkable in their repertoire and expression levels of calcium signaling and binding molecules. My lab studies the functions of voltage-gated calcium channels and intracellular release channels in neuronal signaling, and how these functions are altered by mutations in these channels that cause human disease.

Research in my lab incorporates a multi-faceted approach combining electrophysiology, confocal microscopy, calcium imaging and molecular biology.

Link to Lorenzon Publication List

Recent Publications:

• Lorenzon, N.M., and Beam, K.G. Accessibility of targeted DHPR sites to streptavidin and functional effects of binding on EC coupling. J. Gen. Physiol. 130: 379–388, 2007.
• Lorenzon, N.M., and Beam, K.G. Calcium channelopathies. In: Voltage-gated Calcium Channels (Zamponi GW, ed.), Chapter 16 (22 pp.) Georgetown, TX: Landes Bioscience, 2004.
• Lorenzon, N.M., Haarmann, C.S., Norris, E.E., Papadopoulos, S., and Beam, K.G. Metabolic biotinylation as a probe of supramolecular structure of the triad junction in skeletal muscle. J. Biol. Chem. 279: 44057-44064, 2004.
• Timmons, S.D., Geisert, E., Stewart, A.E., Lorenzon, N.M., and Foehring, R.C. alpha2-Adrenergic receptor-mediated modulation of calcium current in neocortical pyramidal neurons. Brain Res. 1014: 184-196, 2004.
• Lorenzon, N.M., Grabner, M., Suda, N., and Beam, K.G. Structure and targeting of RyR1: Implications from fusion of green fluorescent protein at the amino-terminal. Arch. Biochem. Biophys. 388: 13-17, 2001.
• Price, R.H., Lorenzon, N., and Handa, R.J. Differential expression of estrogen receptor beta splice variants in rat brain: Identification and characterization of a novel variant missing exon 4. Brain Res. Mol. Brain Res. 80: 260-268, 2000.