Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation
Caveolae are spherically shaped nanodomains of the plasma membrane, generated by cooperative assembly of caveolin and cavin proteins. Cavins are cytosolic peripheral membrane proteins with negatively charged intrinsically disordered regions that flank positively charged α-helical regions. Here, we show that the three disordered domains of Cavin1 are essential for caveola formation and dynamic trafficking of caveolae. Electrostatic interactions between disordered regions and α-helical regions promote liquid-liquid phase separation behaviour of Cavin1 in vitro, assembly of Cavin1 oligomers in solution, generation of membrane curvature, association with caveolin-1, and Cavin1 recruitment to caveolae in cells. Removal of the first disordered region causes irreversible gel formation in vitro and results in aberrant caveola trafficking through the endosomal system. We propose a model for caveola assembly whereby fuzzy electrostatic interactions between Cavin1 and caveolin-1 proteins, combined with membrane lipid interactions, are required to generate membrane curvature and a metastable caveola coat.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
|---|---|
| Enthalten in: |
Nature communications - 12(2021), 1 vom: 10. Feb., Seite 931 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Tillu, Vikas A [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Caveolin 1 |
|---|
| Anmerkungen: |
Date Completed 18.03.2021 Date Revised 28.01.2023 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41467-021-21035-4 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM321287673 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM321287673 | ||
| 003 | DE-627 | ||
| 005 | 20231225175502.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41467-021-21035-4 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1070.xml |
| 035 | |a (DE-627)NLM321287673 | ||
| 035 | |a (NLM)33568658 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Tillu, Vikas A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 18.03.2021 | ||
| 500 | |a Date Revised 28.01.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Caveolae are spherically shaped nanodomains of the plasma membrane, generated by cooperative assembly of caveolin and cavin proteins. Cavins are cytosolic peripheral membrane proteins with negatively charged intrinsically disordered regions that flank positively charged α-helical regions. Here, we show that the three disordered domains of Cavin1 are essential for caveola formation and dynamic trafficking of caveolae. Electrostatic interactions between disordered regions and α-helical regions promote liquid-liquid phase separation behaviour of Cavin1 in vitro, assembly of Cavin1 oligomers in solution, generation of membrane curvature, association with caveolin-1, and Cavin1 recruitment to caveolae in cells. Removal of the first disordered region causes irreversible gel formation in vitro and results in aberrant caveola trafficking through the endosomal system. We propose a model for caveola assembly whereby fuzzy electrostatic interactions between Cavin1 and caveolin-1 proteins, combined with membrane lipid interactions, are required to generate membrane curvature and a metastable caveola coat | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Caveolin 1 |2 NLM | |
| 650 | 7 | |a Cavin1 protein, mouse |2 NLM | |
| 650 | 7 | |a Membrane Proteins |2 NLM | |
| 650 | 7 | |a RNA-Binding Proteins |2 NLM | |
| 700 | 1 | |a Rae, James |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Ya |e verfasserin |4 aut | |
| 700 | 1 | |a Ariotti, Nicholas |e verfasserin |4 aut | |
| 700 | 1 | |a Floetenmeyer, Matthias |e verfasserin |4 aut | |
| 700 | 1 | |a Kovtun, Oleksiy |e verfasserin |4 aut | |
| 700 | 1 | |a McMahon, Kerrie-Ann |e verfasserin |4 aut | |
| 700 | 1 | |a Chaudhary, Natasha |e verfasserin |4 aut | |
| 700 | 1 | |a Parton, Robert G |e verfasserin |4 aut | |
| 700 | 1 | |a Collins, Brett M |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature communications |d 2010 |g 12(2021), 1 vom: 10. Feb., Seite 931 |w (DE-627)NLM199274525 |x 2041-1723 |7 nnns |
| 773 | 1 | 8 | |g volume:12 |g year:2021 |g number:1 |g day:10 |g month:02 |g pages:931 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41467-021-21035-4 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 12 |j 2021 |e 1 |b 10 |c 02 |h 931 | ||