Charles S. Zuker

Gee Fizz: The next time you enjoy a carbonated beverage, you can do so with an enhanced understanding of the molecular mechanism that provides its distinctive flavor sensation. Chandrashekar et al. (p. 443 ) genetically ablated specific sets of taste cells in mice and found that the sensation of CO ₂ was lost in animals lacking taste cells that sense sour flavors. A screen for genes specifically expressed in these cells revealed the gene encoding carbonic anhydrase 4, which catalyzes hydration of CO ₂ to form bicarbonate and free protons. Knockout animals not expressing the carbonic anhydrase 4 gene also showed diminished sensation of CO ₂ . The protons produced by the enzyme appear to be the actual molecules sensed by the sour-sensitive cells. This process, combined with tactile sensations, appears to be the source of the popular fizzy sensation.

An investigation into how poikilothermic organisms are able to maintain highly effective mechanical responses finds that a protein called Spam forms an extracellular shield that guards mechanosensory neurons from environmental insult. Spam also enables cells to resist physically and chemically induced deformation. Maintaining cell shape and tone is crucial for the function and survival of cells and tissues. Mechanotransduction relies on the transformation of minuscule mechanical forces into high-fidelity electrical responses1,2,3. When mechanoreceptors are stimulated, mechanically sensitive cation channels open and produce an inward transduction current that depolarizes the cell. For this process to operate effectively, the transduction machinery has to retain integrity and remain unfailingly independent of environmental changes. This is particularly challenging for poikilothermic organisms, where changes in temperature in the environment may impact the function of mechanoreceptor neurons. Thus, we wondered how insects whose habitat might quickly vary over several tens of degrees of temperature manage to maintain highly effective mechanical senses. We screened for Drosophila mutants with defective mechanical responses at elevated ambient temperatures, and identified a gene, spam, whose role is to protect the mechanosensory organ from massive cellular deformation caused by heat-induced osmotic imbalance. Here we show that Spam protein forms an extracellular shield that guards mechanosensory neurons from environmental insult. Remarkably, heterologously expressed Spam protein also endowed other cells with superb defence against physically and chemically induced deformation. We studied the mechanical impact of Spam coating and show that spam-coated cells are up to ten times stiffer than uncoated controls. Together, these results help explain how poikilothermic organisms preserve the architecture of critical cells during environmental stress, and illustrate an elegant and simple solution to such challenge.

Eyes differ markedly in the animal kingdom, and are an extreme example of the evolution of multiple anatomical solutions to light detection and image formation. A salient feature of all photoreceptor cells is the presence of a specialized compartment (disc outer segments in vertebrates, and microvillar rhabdomeres in insects), whose primary role is to accommodate the millions of light receptor molecules required for efficient photon collection. In insects, compound eyes can have very different inner architectures^1,2,3. Fruitflies and houseflies have an open rhabdom system, in which the seven rhabdomeres of each ommatidium are separated from each other and function as independent light guides. In contrast, bees and various mosquitoes and beetle species have a closed system, in which rhabdomeres within each ommatidium are fused to each other, thus sharing the same visual axis. To understand the transition between open and closed rhabdom systems, we isolated and characterized the role of Drosophila genes involved in rhabdomere assembly. Here we show that Spacemaker, a secreted protein expressed only in the eyes of insects with open rhabdom systems, acts together with Prominin and the cell adhesion molecule Chaoptin to choreograph the partitioning of rhabdomeres into an open system. Furthermore, the complete loss of spacemaker (spam) converts an open rhabdom system to a closed one, whereas its targeted expression to photoreceptors of a closed system markedly reorganizes the architecture of the compound eyes to resemble an open system. Our results provide a molecular atlas for the construction of microvillar assemblies and illustrate the critical effect of differences in a single structural protein in morphogenesis.

In recent years the molecular mechanisms of three of the five basic taste sensations in mammals have been identified: sweet, bitter and umami (monosodium glutamate). The others, sour (or 'acid') and salt, were elusive. Now the cells and a candidate receptor mediating sour taste have been identified. PKD2L1, a polycystic kidney disease-like ion channel, is proposed to act as part of the mammalian sour taste receptor, and shown to define the population of cells on the tongue required for sour taste. PKD2L1 is also found in neurons around the central canal of the spinal cord that trigger action potentials in response to a fall in extracellular pH. These cells could be long-sought components of the cerebrospinal fluid chemosensory system. This work points to a common basis for acid sensing in very different physiological settings. On the cover, tongue tissue with taste receptor cells labelled red for sour sensing and green for sweet, umami and bitter. Mammals taste many compounds yet use a sensory palette consisting of only five basic taste modalities: sweet, bitter, sour, salty and umami (the taste of monosodium glutamate)1,2. Although this repertoire may seem modest, it provides animals with critical information about the nature and quality of food. Sour taste detection functions as an important sensory input to warn against the ingestion of acidic (for example, spoiled or unripe) food sources1,2,3. We have used a combination of bioinformatics, genetic and functional studies to identify PKD2L1, a polycystic-kidney-disease-like ion channel4, as a candidate mammalian sour taste sensor. In the tongue, PKD2L1 is expressed in a subset of taste receptor cells distinct from those responsible for sweet, bitter and umami taste. To examine the role of PKD2L1-expressing taste cells in vivo, we engineered mice with targeted genetic ablations of selected populations of taste receptor cells. Animals lacking PKD2L1-expressing cells are completely devoid of taste responses to sour stimuli. Notably, responses to all other tastants remained unaffected, proving that the segregation of taste qualities even extends to ionic stimuli. Our results now establish independent cellular substrates for four of the five basic taste modalities, and support a comprehensive labelled-line mode of taste coding at the periphery5,6,7,8,9,10. Notably, PKD2L1 is also expressed in specific neurons surrounding the central canal of the spinal cord. Here we demonstrate that these PKD2L1-expressing neurons send projections to the central canal, and selectively trigger action potentials in response to decreases in extracellular pH. We propose that these cells correspond to the long-sought components of the cerebrospinal fluid chemosensory system11. Taken together, our results suggest a common basis for acid sensing in disparate physiological settings.

A major challenge in the study of intracellular signaling has been the elucidation of the physical and biological principles by which the network of signaling molecules is assembled to execute signaling programs. In their Perspective, Zuker et al. address recent work focusing on the organization of signaling components into macromolecular assemblies, in particular, the tyrosine kinase and G protein-coupled receptor pathways.