The Hippo Pathway Regulates Caveolae Expression and Mediates Flow Response via Caveolae. Curr Biol 2019 01 21;29(2):242-255.e6
Date
01/01/2019Pubmed ID
30595521Pubmed Central ID
PMC6345631DOI
10.1016/j.cub.2018.11.066Scopus ID
2-s2.0-85060027631 20 CitationsAbstract
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 CGAuthor
Brian A. Link PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCaveolae
HEK293 Cells
Humans
Protein-Serine-Threonine Kinases
Signal Transduction
Zebrafish
Zebrafish Proteins
