The Regulation of the Hippo Pathway by Intercellular Junction Proteins

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• The Hippo pathway is a conserved signaling network controlling organ size by regulating cell proliferation, apoptosis, and differentiation.
• Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are key downstream effectors, with their activity inhibited by upstream kinases.
• External stimuli like mechanical forces and cell-cell contact modulate Hippo pathway activity, influencing YAP/TAZ localization and function.

Purpose of the Study:

• To review the role of intercellular junction proteins in Hippo pathway activation.
• To highlight recent findings on desmosomal components, specifically desmoglein-3 (DSG3), in regulating YAP signaling.
• To elucidate the molecular mechanisms controlling YAP/TAZ subcellular localization and activity.

Main Methods:

• Literature review of Hippo pathway regulation.
• Analysis of studies investigating intercellular junctions (adherens, tight, desmosomes).
• Focus on experimental data concerning desmoglein-3 (DSG3) and its impact on YAP/TAZ.

Main Results:

• Intercellular junction-associated proteins, including adherens and tight junctions, play a role in Hippo pathway activation.
• Desmosomal components, particularly desmoglein-3 (DSG3), are implicated in regulating YAP signaling.
• DSG3 influences YAP phosphorylation and subcellular translocation, thereby modulating Hippo pathway output.

Conclusions:

• Intercellular junctions are critical regulators of the Hippo pathway.
• Desmoglein-3 (DSG3) emerges as a key player in controlling YAP/TAZ activity through modulation of signaling and localization.
• Understanding these interactions provides insights into tissue homeostasis and disease pathogenesis.