Salt, Fat, Acid, Heat: Modulators of Signal Transduction

Abstract

Signal transduction pathways are heavily dependent on interactions with the cellular environment. The same environmental elements that make food tasty (salt, fat, acid, heat) have profound impacts on many other aspects of protein function. Transducing sensory information involves a change in receptor confirmation on a sensory neuron/end organ (e.g. taste bud), which allows perception of salt, fat, acid and heat. Beyond our perception, however, are the wide‐ranging effects that these environmental elements have on the intracellular signal transduction pathways which impacts every aspect of cell, tissue, organ and organism function. The proteins constituting signalling pathways are constantly receiving environmental information including ionic charges (salt), hydrophobicity (fat), protonation state (acid) and thermal energy (heat). Key Concepts Signal transduction pathways can be altered by environmental fluctuations. Salts dissociate into their separate ionic forms. Regulating ion type and concentration are important for maintaining protein structure, enzyme activity, protein interactions and controlling ion channels. Lipid modifications can influence a protein's microdomain localisation to its target cell and impact ease of intracellular or extracellular diffusion. Fluctuations in pH alter the protonation state of proteins and ion channels which can impact its specificity, affinity to binding partners, structural dynamics and the pathways that are activated. Temperature changes (e.g. extreme hot or cold) can inactivate and denature proteins generally but specifically may gate temperature‐sensitive ion channels [i.e. transient receptor potential ( TRP ) channels]. Changes in temperature can also reveal gain or loss of function phenotypes for mutations that confer less severe phenotypes at physiological temperatures, as exemplified by numerous temperature‐sensitive alleles used in genetics and cell biology experiments.