Journal Club: Neuoscience, Physiology and Biochemistry
NEUROSCIENCE: RIM-binding protein links synaptic homeostasis to the stabilization and replenishment of high release probability vesicles. Müller, M., Genç, Ö., and Davis, G.W. Neuron. 2015. Epub ahead of print
Control of muscles requires many levels of careful regulation, including at the synapse between the muscle-innervating nerve and the muscle fiber. The nerve ending responds to changes in sensitivity of the muscle by tuning its own release of neurotransmitters.
Previous research has found the mechanism for this self-tuning involves both adjustments in calcium influx and the size of the readily releasable pool of vesicles. Whether, and how, these two processes were co-regulated was unclear, but in this paper the authors find a unifying element.
Performing research in flies, they found that a disabling mutation of RIM-binding protein (RBP) leads to a tenfold decrease in calcium sensitivity at baseline. Moreover, homeostatic adjustments in both calcium sensitivity and the size of the rapidly releasable vesicle pool are dependent on this protein.
NEUROSCIENCE: Sensory detection of food rapidly modulates arcuate feeding circuits. Chen, Y. et al. (Knight, Z.A.). Cell. 2015. Epub ahead of print.
When it comes to how much to eat, for most of evolution the only risk was to fall short. Today, however, humans increasingly suffer from the opposite problem.
The regulation of hunger involves the opposing activity of two groups of neurons: the AgRP neurons promote appetite, whereas the POMC neurons inhibit it. In this paper, Chen and colleagues provide new insights into how the circuit rapidly responds to outside stimuli.
Observing the activity of these two groups of neuron in awake mice, they found that the activity of these neurons changes after the animal has encountered food but before any has been eaten. The anticipated tastiness of the food influenced the strength of the effect. The authors suggest that these neurons control not only food consumption but also foraging.
PHYSIOLOGY: Gαi/o coupled receptor signaling restricts pancreatic β-cell expansion: Berger, M. et al. (German, M.S.). PNAS. 2015. Epub ahead of print.
Nearly one in 10 Americans has diabetes, the large majority having type 2 diabetes, and the prevalence has been increasing.
Type 2 diabetes is associated with decreased amount of β cells, which produce insulin. Members of the Gαi/o family of G protein-coupled receptors have already been implicated in insulin release by β cells, but their role in β cell mass was unclear.
Here, the authors show that in mice Gi GPCRs act to rein in β cell proliferation, especially around birth. They found that increased Gi-GPCR activity leads to decreased proliferation leading to less β cell mass, whereas inhibiting these GPCRs led to increased β cell mass and glucose homeostasis. Selective deletion of GPCRs revealed that ADRA2A is a critical controller of β cell proliferation.
BIOCHEMISTRY: A nucleotide-driven switch regulates flanking DNA length sensing by a dimeric chromatin remodeler. Leonard, J.D. and Narlikar, G.J. Mol Cell. 2015. Epub ahead of print.
The ways in which shaping chromatin shapes cell fate are being documented in ever greater detail, with the massive data released by the Human Epigenome Roadmap Consortium a couple of weeks ago marking only the latest large-scale assay.
The ways in which proteins sense and modify these epigenetic marks remain far from fully understood, however. The ACF protein complex supports the formation of silent chromatin through how it spaces nucleosomes, but how it did this remained hazy.
In this article, the authors find that the ACF component SNF2h, which senses the length of DNA flanking a nucleosome, undergoes a nucleotide-dependent change. One conformation supports binding to flanking DNA while the other supports binding of the nucleosome core. The authors suggest that these activities might therefore be regulated independently.
