Jeon, N. L. | Search bioRxiv

bioRxiv2018

Optimal diameter reduction ratio of acinar airways in human lungs

In the airway network of a human lung, the airway diameter gradually decreases through multiple branching. The diameter reduction ratio of the conducting airways that transport gases without gas exchange is 0.79, but this reduction ratio changes to 0.94 in acinar airways beyond transitional bronchioles. While the reduction in the conducting airways was previously rationalized on the basis of Murrays law, our understanding of the design principle behind the acinar airways has been far from clear. Here we elucidate that the change in gas transfer mode is responsible for the transition in the diameter reduction ratio. The oxygen transfer rate per unit surface area is maximized at the observed geometry of acinar airways, which suggests the minimum cost for the construction and maintenance of the acinar airways. The results revitalize and extend the framework of Murrays law over an entire human lung.

bioengineering↗

bioRxiv2018

Compartmentalized nonsense-mediated mRNA decay regulates synaptic plasticity and cognitive function via GluR1 signaling

Synaptic plasticity relies on new protein synthesis in dendrites that involves the selective translation of specific mRNAs. This requires a tight control of mRNA levels in dendrites. Consistently, RNA translation and degradation pathways have been recently linked to neurodevelopmental and neuropsychiatric diseases, suggesting a role for RNA regulation in synaptic plasticity and cognition. Despite being the only RNA regulatory pathway that is associated with multiple mental illnesses, the Nonsense-Mediated mRNA Decay (NMD) pathway presents an unexplored regulatory mechanism for synaptic function and plasticity. NMD is a highly conserved and selective RNA degradation pathway that exerts its function in a cell- and spatiotemporally-specific manner. Here, we show that neuron-specific disruption of NMD in adulthood attenuates learning, memory, hippocampal LTP, and potentiates perseverative/repetitive behavior. While it is known that local translation of specific mRNAs in dendrites enables synaptic plasticity, the tightly-controlled mechanisms that regulate local quantity of specific mRNAs remains poorly understood. We report that the NMD pathway operates within dendrites to regulate GluR1 surface levels. Specifically, NMD modulates the internalization of GluR1 and promotes its local synthesis in dendrites. We identified AMPK as a mechanistic substrate for NMD that contributes to the NMD-mediated regulation of GluR1 by limiting total GluR1 levels. These data establish that NMD regulates synaptic plasticity, cognition, and local protein synthesis in dendrites, providing fundamental insight into the neuron-specific function of NMD within the brain.

neuroscience↗