Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

The Hippo Pathway Regulates Caveolae Expression and Mediates Flow Response via Caveolae. Curr Biol 2019 01 21;29(2):242-255.e6

Date

01/01/2019

Pubmed ID

30595521

Pubmed Central ID

PMC6345631

DOI

10.1016/j.cub.2018.11.066

Scopus ID

2-s2.0-85060027631   20 Citations

Abstract

The Hippo pathway plays major roles in development, regeneration, and cancer. Its activity is tightly regulated by both diffusible chemical ligands and mechanical stimuli. The pathway consists of a series of kinases that can control the sub-cellular localization and stability of YAP or TAZ, homologous transcriptional co-factors. Caveolae, small (60-100 nm) bulb-like invaginations of the plasma membrane, are comprised predominantly of caveolin and cavin proteins and can respond to mechanical stimuli. Here, we show that YAP/TAZ, the major transcriptional mediators of the Hippo pathway, are critical for expression of caveolae components and therefore caveolae formation in both mammalian cells and zebrafish. In essence, without YAP/TAZ, the cell loses an entire organelle. CAVEOLIN1 and CAVIN1, the two essential caveolar genes, are direct target genes of YAP/TAZ, regulated via TEA domain (TEAD) transcription factors. Notably, YAP/TAZ become nuclear enriched and facilitate target gene transcription in cells with diminished levels of caveolae. Furthermore, caveolar-mediated shear stress response activates YAP/TAZ. These data link caveolae to Hippo signaling in the context of cellular responses to mechanical stimuli and suggest activity-based feedback regulation between components of caveolae and the outputs of the Hippo pathway.

Author List

Rausch V, Bostrom JR, Park J, Bravo IR, Feng Y, Hay DC, Link BA, Hansen CG

Author

Brian A. Link PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Caveolae
HEK293 Cells
Humans
Protein-Serine-Threonine Kinases
Signal Transduction
Zebrafish
Zebrafish Proteins
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0