Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Artículo científico |
| Language: | en |
| Published: |
Proceedings of the National Academy of Sciences of the United States of America
2025
|
| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40424130/ |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Table of Contents:
- Dynamic early recruitment of GAK-Hsc70 regulates coated pit maturation. He, Zhangping Zuo, Peiyao Xu, Peiliu Yuan, Haozhi Bhave, Madhura Wei, Xiangying Yang, Ziyan Han, Lu Schmid, Sandra L Chen, Zhiming HSC70 Heat-Shock Proteins Endocytosis Humans Coated Pits, Cell-Membrane Clathrin Clathrin-Coated Vesicles Animals Intracellular Signaling Peptides and Proteins Clathrin-mediated endocytosis (CME) begins with the assembly of clathrin onto the plasma membrane. These structures grow and stabilize to form clathrin-coated pits (CCPs), which invaginate and accumulate cargo. Finally, through membrane fission, CCPs detach to form clathrin-coated vesicles (CCVs). Mechanisms governing the transition of CCPs from flat-to-curved structures have been a matter of debate. GAK and its chaperone protein, Hsc70, are well known to mediate clathrin release from CCVs, and several studies have observed a late burst of GAK recruitment as CCVs form. Other studies have proposed that early recruitment of GAK-Hsc70 could function to provide the necessary energy source to remodel nascent flat clathrin lattices, replacing hexagons with pentagons and enabling a gain of curvature and invagination of the growing CCP; however, direct functional evidence is lacking. Here, we show that GAK knockdown inhibits CCP stabilization and invagination. Furthermore, mutations in the J domain of GAK that abolish Hsc70 recruitment to and activation at CCPs lead to the accumulation of GAK at CCPs, hinder CCP stabilization and invagination, and result in a striking increase in the proportion of highly transient, abortive CCPs. These findings support the hypothesis that GAK-Hsc70 promotes the turnover and remodeling of nascent clathrin assemblies required for curvature development during CME.