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Tuning in the Hippocampal Theta Band In Vitro: Methodologies for Recording from the Isolated Rodent Septohippocampal Circuit
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Yorkie/YAP Interactors: Fine-Tuning the Hippo Pathway Output

Alexey Veraksa1, Kenneth H Moberg2

  • 1Department of Biology, University of Massachusetts Boston, Boston, Massachusetts 02125, USA alexey.veraksa@umb.edu kmoberg@emory.edu.

Cold Spring Harbor Perspectives in Biology
|August 10, 2026
PubMed

Insights

The Hippo signaling pathway is fine-tuned by additional regulators, or "tuners," that control the activity of key effectors like Yorkie (Yki)/Yes-associated protein 1 (YAP1). These tuners impact Yki/YAP1 levels and nuclear functions, influencing cellular outcomes.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Signal Transduction

Background:

  • The Hippo signaling pathway is a crucial regulator of organ size and cell proliferation.
  • Canonical Hippo pathway components, including MST and LATS kinases, control the nuclear localization and activity of effectors like YAP1/TAZ.
  • Emerging evidence indicates additional regulators modulate Hippo pathway activity.

Purpose of the Study:

  • To review the diverse "tuners" that fine-tune Hippo pathway activity.
  • To highlight the mechanisms by which these tuners regulate YAP1/TAZ.
  • To discuss the implications of these regulatory networks for cellular outcomes.

Main Methods:

  • Literature review of studies in flies and mammals.
  • Analysis of protein-protein interactions, including PPxY motif/WW domain interactions.
  • Examination of subcellular localization and degradation pathways.

Main Results:

  • Multiple "tuners" associate with YAP1/TAZ at endosomal membranes, the cell cortex, and in the nucleus.
  • These tuners regulate YAP1/TAZ turnover, nucleocytoplasmic shuttling, and degradation.
  • Nuclear tuners direct specific cellular outcomes through unique transcriptional programs with YAP1/TAZ.

Conclusions:

  • Hippo pathway regulation is more complex than previously thought, involving numerous "tuners" that modulate YAP1/TAZ.
  • These tuners influence YAP1/TAZ levels and activity through sequestration and degradation.
  • Understanding the coordination of these tuners is crucial for deciphering Hippo pathway functions in vivo.

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