No abstract

The olfactory system relies on precise circuitry connecting olfactory sensory neurons (OSNs) and appropriate relay and processing neurons of the olfactory bulb (OB). In mammals, the exact correspondence between specific olfactory receptor types and individual glomeruli enables a spatially precise map of glomerular activation that corresponds to distinct odors. However, the mechanisms that govern the establishment and maintenance of the glomerular circuitry are largely unknown. Here we show that high levels of Sonic Hedgehog (Shh) signaling at multiple sites enable refinement and maintenance of olfactory glomerular circuitry. Mice expressing a mutant version of Shh (ShhAla/Ala), with impaired binding to proteoglycan co-receptors, exhibit disproportionately small olfactory bulbs containing fewer glomeruli. Notably, in mutant animals the correspondence between individual glomeruli and specific olfactory receptors is lost, as olfactory sensory neurons expressing different olfactory receptors converge on the same glomeruli. These deficits arise at late stages in post-natal development and continue into adulthood, indicating impaired pruning of erroneous connections within the olfactory bulb. In addition, mature ShhAla/Ala mice exhibit decreased proliferation in the subventricular zone (SVZ), with particular reduction in neurogenesis of calbindin-expressing periglomerular cells. Thus, Shh interactions with proteoglycan co-receptors function at multiple locations to regulate neurogenesis and precise olfactory connectivity, thereby promoting functional neuronal circuitry.

Because 14-3-3 binds to proteins that are crucial to cardiac functions and heart health, the cardiac 14-3-3 interactome may be a potential therapeutic target in cardiovascular metabolic and proteostatic disease states, as it already is in cancer therapy.

No abstract

Cells must precisely orchestrate thousands of reactions in both time and space. Yet reaction kinetics are highly dependent on uncontrollable environmental conditions such as temperature. Here, we report a novel mechanism by which budding yeast influence reaction rates through adjustment of intracellular viscosity. This "viscoadaptation" is achieved by production of two carbohydrates, trehalose and glycogen, which combine to create a more viscous cellular environment in which biomolecules retain solubility. We demonstrate that viscoadaptation functions as both an acute response to temperature increase as well as a homeostatic mechanism, allowing cells grown at temperatures spanning from 22℃ to 40℃ to maintain equivalent rates of intracellular diffusion and diffusion-controlled chemical reactions. Multiple conditions that lower ATP trigger viscoadaptation, suggesting that viscoadaptation may be a general cellular response to low energy. Viscoadaptation reveals viscosity to be a tunable property of cells through which they can regulate diffusion-controlled processes dynamically in response to a changing environment.