Taste sensor keeps protein organized in flies

A set of genes that promote the sensation of sweetness are also important for protein management during fly development, according to a new study led by the University of Bristol and colleagues, published today (July 21) in the open access journal PLOS Biology. These findings broaden the understanding of key processes in successful development and suggest a link between taste-related genes and impaired protein aggregation.

Protein homeostasis or proteostasis, is a set of processes that maintains cellular proteins in a functional state and removes damaged proteins that cannot be repaired. Ribosomes are multi-protein molecular machinery that synthesizes proteins and mutations in genes encoding ribosomal proteins not only impair protein synthesis but also impair proteostasis, leading to chronic proteotoxic stress. That stress, in turn, has a number of cellular consequences and results in delayed development and other irregularities.

To better understand the disturbances caused by such impaired proteostasis, the authors compared gene expression in normal versus ribosomal protein mutant flies during the pupal developmental stage. Unexpectedly, they discovered that a group of genes encoding six gustatory (taste) receptors, called the Gr64 gene, was upregulated in the mutant cells.

This finding was unexpected because Gr64 receptors were previously known to be present in adult fly neurons, where they help animals sense sugars, fatty acids and glycerol. In flies mutant ribosomal proteins with only one (rather than two) working copies of the Gr64 gene, cell death is increased through a process called apoptosis. Complete deletion of the Gr64 gene induces some morphological defects in ribosomal mutants, but has little or no effect in cells with normal ribosomal proteins.

Cells carrying mutant ribosomal proteins are at a disadvantage compared to normal cells and are often eliminated in developing tissues where both occur. Mutants carrying only one set of Gr64 genes did even worse, the authors found, losing out to normal cells to a greater extent. When Gr64 protein levels were variably and quantitatively reduced, the team showed that the most direct reduction effect was on proteasome and autophagosome function, two distinct routes by which damaged proteins are excreted and recycled.

The relationship between the promotion of proteostasis and the sense of taste is most likely through the molecular mechanism of the protein Gr64, which regulates calcium flow; Changes in calcium levels are used as signal transducers in sensory cells and also regulate various proteostatic processes, including proteosome function and autophagy. Interestingly, disorganized and misplaced taste and olfactory receptors have been detected in affected brain tissue in several human diseases characterized by loss of protein homeostasis, including Alzheimer’s disease and Parkinson’s disease.

Professor Eugenia Piddini, Wellcome Trust Senior Research Fellow in the School of Cellular and Molecular Medicine at the University of Bristol, who led the study, said: “Our work demonstrates that gustatory receptors play a previously unknown role in maintaining protein homeostasis during development in flight and points to more generally towards an association between calcium-modulating proteins and impaired protein aggregation and proteotoxic stress.”

Professor Piddini added: “What I find really interesting about our findings is that they underscore what little we understand about how cells adapt to cope with proteotoxic stress. Our experimental strategy could be further used as a way to search for and discover additional new proteostatic genes.”

Michael Baumgartner, co-author concludes: “These findings emphasize an important theme in cell biology: context is everything. It’s easy to look at the name ‘gustatory receiver’ and think that’s the end of the story, but evolution can and will reuse almost anything if it ends up being profitable. This highlights the possibility that apparently highly specialized gustatory receptors may be more flexible than previously thought. ”

Paper:

‘Gr64 gustatory receptor cluster promotes epithelial cell survival and proteostasis in Drosophila’ by ME Baumgartner, E Piddini et al in PLOS Biology [open access]

#Taste #sensor #protein #organized #flies