Regulation of YAP activity by nuclear G-actin binding.

Area of Science:

• Molecular and Cellular Biology
• Biochemistry
• Biophysics

Background:

• The Yes-associated protein (YAP) is a key regulator in the Hippo pathway, controlling tissue size and cellular functions like proliferation and differentiation.
• YAP activity is influenced by the actin cytoskeleton through various biomechanical cues.
• YAP (Yes-associated protein) and TAZ (transcriptional co-activator with PDZ-binding motif) are paralogs involved in Hippo pathway signaling.

Purpose of the Study:

• To investigate the direct interaction between YAP and the actin cytoskeleton.
• To determine the functional significance of YAP-actin binding in cellular processes and transcriptional regulation.

Main Methods:

• Identification of YAP actin-binding sites using biochemical assays.
• Site-directed mutagenesis to disrupt identified binding sites.
• Assessment of YAP transcriptional activity and interaction with TEAD (TEA/ATTS domain) transcription factors.

Main Results:

• YAP (Yes-associated protein) was identified as a novel G-actin binding protein.
• Three high-affinity actin-binding sites were mapped to the N-terminus of YAP.
• Actin binding to YAP is essential for its transcriptional co-activator function with TEAD (TEA/ATTS domain) and regulation of TEAD target genes.

Conclusions:

• Direct binding of G-actin to YAP is a prerequisite for YAP's transcriptional activity and function.
• A dynamic ternary complex involving TEAD (TEA/ATTS domain), YAP, and actin is proposed to be essential for transcription.