PUBLICATION
The Hippo Pathway Regulates Caveolae Expression and Mediates Flow Response via Caveolae
- Authors
- Rausch, V., Bostrom, J.R., Park, J., Bravo, I.R., Feng, Y., Hay, D.C., Link, B.A., Hansen, C.G.
- ID
- ZDB-PUB-190101-2
- Date
- 2018
- Source
- Current biology : CB 29(2): 242-255.e6 (Journal)
- Registered Authors
- Feng, Yi, Link, Brian
- Keywords
- CAV1, CAVIN1, Hippo pathway, TAZ, YAP, caveolae, extra cellular matrix, mechanotransduction, shear stress
- MeSH Terms
-
- Animals
- Caveolae/metabolism*
- HEK293 Cells
- Humans
- Protein Serine-Threonine Kinases/genetics*
- Protein Serine-Threonine Kinases/metabolism
- Signal Transduction/physiology*
- Zebrafish/genetics
- Zebrafish/physiology*
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 30595521 Full text @ Curr. Biol.
Citation
Rausch, V., Bostrom, J.R., Park, J., Bravo, I.R., Feng, Y., Hay, D.C., Link, B.A., Hansen, C.G. (2018) The Hippo Pathway Regulates Caveolae Expression and Mediates Flow Response via Caveolae. Current biology : CB. 29(2):242-255.e6.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping