My research interests center around G protein-coupled receptor function, particularly metabotropic glutamate receptors (mGluRs), and ion channel modulation in neurons. Naturally, this work has led me toward an interest in heterotrimeric G proteins, G protein-coupled receptors and factors that modulate G protein signaling, such as the Regulators of G protein Signaling (RGS) proteins (see Kammermeier and Ikeda, 1999, Neuron 22:819). I have also become interested in the Homer family of scaffolding proteins, which I have shown to be important in the function and sub-cellular localization of metabotropic glutamate receptors (Kammermeier et al., 2000, Journal of Neuroscience 220:7238; Kammermeier, 2005, BMC Neuroscience 7:1). In the long term, my goal is to understand the mechanisms of regulation, localization and signaling that impart specificity to the various mGluRs, and how regulation of mGluR signaling alters synaptic strength in the nervous system.
In my laboratory, two basic experimental approaches are used. The first utilizes primary cultures of isolated SCG neurons for electrophysiological, molecular biological, immunofluorescence and RT-PCR experiments. The main technique used in this system is to examine the well-characterized ion channel modulatory pathways using patch-clamp electro-physiology as an assay for G protein coupled receptor activity. The neurons can be made to express various heterologous proteins (including mGluRs) via intranuclear injection of cDNA. I have recently used this system to examine mGluR-G protein coupling specificity, mGluR desensitization and the regulation of mGluR signaling and trafficking by various associated proteins.
The second approach is to use native neuronal cells. Currently, we are working with both primary isolated ON Bipolar cells from the rat retina and with rat hippocampal neurons to examine G protein coupling of mGluR6 and the effects of Homer protein regulation of mGluR5 at synapses, respectively. These systems allow us to ask questions about the physiological relevance in parallel with the more tractable, highly amenable SCG system described above.
Finally, we are beginning to incorporate other fluorescence-based techniques such as total internal reflection fluorescence (TIRF) microscopy (Kammermeier, 2005, BMC Neuroscience 7:1) to examine protein distribution in or very near the cell membrane.