Phosphorylation of the small heat shock protein HspB1 regulates cytoskeletal recruitment and cell motility
The small heat shock protein HspB1, also known as Hsp25/27, is a ubiquitously expressed molecular chaperone that responds to mechanical cues. Uniaxial cyclic stretch activates the p38 mitogen-activated protein kinase (MAPK) signaling cascade and increases the phosphorylation of HspB1. Similar to the...
Uloženo v:
| Vydáno v: | Molecular biology of the cell Ročník 33; číslo 11; s. ar100 |
|---|---|
| Hlavní autoři: | , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
15.09.2022
|
| ISSN: | 1939-4586, 1939-4586 |
| On-line přístup: | Zjistit podrobnosti o přístupu |
| Tagy: |
Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
|
| Shrnutí: | The small heat shock protein HspB1, also known as Hsp25/27, is a ubiquitously expressed molecular chaperone that responds to mechanical cues. Uniaxial cyclic stretch activates the p38 mitogen-activated protein kinase (MAPK) signaling cascade and increases the phosphorylation of HspB1. Similar to the mechanosensitive cytoskeletal regulator zyxin, phospho-HspB1 is recruited to features of the stretch-stimulated actin cytoskeleton. To evaluate the role of HspB1 and its phosphoregulation in modulating cell function, we utilized CRISPR/Cas9-edited HspB1-null cells and determined they were altered in behaviors such as actin cytoskeletal remodeling, cell spreading, and cell motility. In our model system, expression of WT HspB1, but not nonphosphorylatable HspB1, rescued certain characteristics of the HspB1-null cells including the enhanced cell motility of HspB1-null cells and the deficient actin reinforcement of stretch-stimulated HspB1-null cells. The recruitment of HspB1 to high-tension structures in geometrically constrained cells, such as actin comet tails emanating from focal adhesions, also required a phosphorylatable HspB1. We show that mechanical signals activate posttranslational regulation of the molecular chaperone, HspB1, and are required for normal cell behaviors including actin cytoskeletal remodeling, cell spreading, and cell migration.The small heat shock protein HspB1, also known as Hsp25/27, is a ubiquitously expressed molecular chaperone that responds to mechanical cues. Uniaxial cyclic stretch activates the p38 mitogen-activated protein kinase (MAPK) signaling cascade and increases the phosphorylation of HspB1. Similar to the mechanosensitive cytoskeletal regulator zyxin, phospho-HspB1 is recruited to features of the stretch-stimulated actin cytoskeleton. To evaluate the role of HspB1 and its phosphoregulation in modulating cell function, we utilized CRISPR/Cas9-edited HspB1-null cells and determined they were altered in behaviors such as actin cytoskeletal remodeling, cell spreading, and cell motility. In our model system, expression of WT HspB1, but not nonphosphorylatable HspB1, rescued certain characteristics of the HspB1-null cells including the enhanced cell motility of HspB1-null cells and the deficient actin reinforcement of stretch-stimulated HspB1-null cells. The recruitment of HspB1 to high-tension structures in geometrically constrained cells, such as actin comet tails emanating from focal adhesions, also required a phosphorylatable HspB1. We show that mechanical signals activate posttranslational regulation of the molecular chaperone, HspB1, and are required for normal cell behaviors including actin cytoskeletal remodeling, cell spreading, and cell migration. |
|---|---|
| Bibliografie: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 1939-4586 1939-4586 |
| DOI: | 10.1091/mbc.E22-02-0057 |