Fat and Dachsous Signaling—Controlling Growth Requires Both Competition and Cooperation: Competitive Interactions at the Cell Cortex Restrict the Ability of an Unusual Protein Complex to Promote Tissue Growth

TL;DR

This paper explains how two proteins, Dachsous and Fat, work together to control tissue growth by regulating a complex that normally promotes growth.

Contribution

The study reveals that Dachsous and Fat can synergistically repress a growth-promoting complex, adding new insight into Hippo signaling regulation.

Findings

The core complex (Dachs, Dlish, Approximated) promotes growth by repressing Warts.

Dachsous and Fat repress the core complex by degrading it or removing it from the cell junction.

Dachsous and Fat can function synergistically to restrict tissue growth.

Abstract

The Hippo signaling pathway plays a key role in organ size control in normal development and tumorigenesis. While many components of this pathway are well understood, its upstream regulation remains unclear. Among the most enigmatic upstream regulators are the protocadherins Dachsous and Fat. These transmembrane proteins regulate a growth‐promoting complex composed of the atypical myosin Dachs, the adaptor protein Dlish, and the palmitoyltransferase Approximated (together termed the core complex). We propose that by default the core complex promotes growth and that Dachsous and Fat, which previously have been thought to act antagonistically, can also function synergistically to repress core complex function and therefore restrict growth. Understanding the molecular mechanisms underlying Dachsous‐Fat signaling offers insight into how multicellular organisms precisely control organ size.

Dachs, Dlish, and Approximated form a core complex at the junctional cortex that promotes growth (On) by repressing Warts. Activity of this complex is repressed (Off) both by Fat‐mediated degradation and by physical removal from the junctional cortex by Dachsous or Fat. Thus, Dachsous and Fat together repress tissue growth.

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