Participants
Carl Hansen
Diversity and Function of Heterotrimeric G Proteins in Antarctic Icefish
Carl A. Hansen, PhD and Janet D. Robishaw. PhD, Department of Biological and Allied Health Sciences, Bloomsburg University, Bloomsburg, PA, and the Weis Center for Research, Geisinger Clinic, Danville, PA.
Organisms have efficient mechanisms to detect and respond to environmental cues. These mechanisms are based on the ability of cells to convert extracellular signals into intracellular messages, a process known as signal transduction. Activation of cell surface receptors by ligand binding ultimately results in a change in the activity of intracellular effector molecules, which in turn, mediate the appropriate cell response to the external signal. A primary mechanism linking activation of cell surface receptors to modulation of intracellular effectors involves a large family of coupling proteins known as heterotrimeric G proteins. Each heterotrimeric G protein is composed of three distinct subunits referred to as the a, b and g subunits. In mammals, 21a subunit genes, 7 b subunit genes, and 12 g subunit genes have been identified, providing the possibility of well over 1000 unique abg combinations. Interestingly, there is a large degree on heterogeneity in each subunit family, but across species, each ortholog is highly conserved. To further understand the evolution and function of these signaling proteins in non-mammalian vertebrates, we are; 1) identifying vertebrate orthologs via data mining genomic data bases; 2) designing PCR primers for cloning and sequencing homologs from non-model organisms; and 3) developing assays to examine how differences in sequence translates in to differences in function. In this respect, studying heterotrimeric G proteins from Antarctic Icefish provides a unique opportunity to assess the effect of temperature on the evolution and function of conserved protein families. While sequence comparisons show conservation of G protein subunit structure across vertebrate species, the cold, but homeothermic environment of the Antarctic waters provides a strong selective pressure for maintaining efficiency of signaling through signal transduction pathways. Understanding how G protein structure and function is modulated to function efficiently at cold temperatures is likely to enhance our understanding of how signaling pathways function in humans and how dysfunctions of these pathways may contribute to human diseases.