Taste sensors keep proteins in flies: New role for adult proteins in development

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

Protein homeostasis, or proteostasis, is a set of processes that maintain cellular proteins in a functional state, and remove damaged proteins that cannot be repaired. Ribosomes are multi-protein molecular machinery that synthesizes proteins, and mutations in the 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 found 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 exist 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.

“Our work demonstrates that gustatory receptors play a previously unknown role in maintaining protein homeostasis during development in flies,” Piddini said, “and points more generally toward an association between calcium-modulating proteins and impaired protein aggregation and proteotoxic stress.”

Piddini adds, “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 used further as a way to search for and discover additional new proteostatic genes.” “

Co-author Michael Baumgartner concludes, “These findings emphasize an important theme in cell biology: context is everything. It’s easy to look at the name ‘gustatory receptor’ and think that’s the end of the story, but evolution can and will reuse almost anything if it ends. “

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