A Hierarchy of Cell Intrinsic and Target-Derived Homeostatic Signaling

SummaryHomeostatic control of neural function can be mediated by the regulation of ion channel expression, neurotransmitter receptor abundance, or modulation of presynaptic release. These processes can be implemented through cell autonomous or intercellular signaling. It remains unknown whether different forms of homeostatic regulation can be coordinated to achieve constant neural function. One way to approach this question is to confront a simple neural system with conflicting perturbations and determine whether the outcome reflects a coordinated, homeostatic response. Here, we demonstrate that two A-type potassium channel genes, shal and shaker, are reciprocally, transcriptionally coupled to maintain A-type channel expression. We then demonstrate that this homeostatic control of A-type channel expression prevents target-dependent, homeostatic modulation of synaptic transmission. Thus, we uncover a homeostatic mechanism that reciprocally regulates A-type potassium channels, and we define a hierarchical relationship between cell-intrinsic control of ion channel expression and target-derived homeostatic control of synaptic transmission.

► A genetic screen identifies K-channel mutations that block synaptic homeostasis
► shal and shaker are reciprocally coupled to maintain A-type channel expression
► Homeostatic modulation of A-type channel expression occludes synaptic homeostasis
► We define a hierarchy of cell-intrinsic and target-derived homeostatic mechanisms