Composition and Control of a Deg/ENaC Channel during Presynaptic Homeostatic Plasticity

Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Brian O. Orr, David Gorczyca, Meg A. Younger, Lily Y. Jan, Yuh-Nung Jan, Graeme W. Davis
The homeostatic control of presynaptic neurotransmitter release stabilizes information transfer at synaptic connections in the nervous system of organisms ranging from insect to human. Presynaptic homeostatic signaling centers upon the regulated membrane insertion of an amiloride-sensitive degenerin/epithelial sodium (Deg/ENaC) channel. Elucidating the subunit composition of this channel is an essential step toward defining the underlying mechanisms of presynaptic homeostatic plasticity (PHP). Here, we demonstrate that the ppk1 gene encodes an essential subunit of this Deg/ENaC channel, functioning in motoneurons for the rapid induction and maintenance of PHP. We provide genetic and biochemical evidence that PPK1 functions together with PPK11 and PPK16 as a presynaptic, hetero-trimeric Deg/ENaC channel. Finally, we highlight tight control of Deg/ENaC channel expression and activity, showing increased PPK1 protein expression during PHP and evidence for signaling mechanisms that fine tune the level of Deg/ENaC activity during PHP.

Graphical abstract

Teaser

Orr et al. define the subunit composition of an essential Deg/ENaC channel that controls the rapid induction and sustained expression of presynaptic homeostatic plasticity. The demonstration that PPK1 incorporates into DEG/ENaC channels with diverse physiological activities highlights the potential for tremendous DEG/ENaC channel diversity in Drosophila.


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