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| Format: | Artículo científico |
| Language: | en |
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Proceedings of the National Academy of Sciences of the United States of America
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40424130/ |
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| _version_ | 1868266198744956928 |
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| author | He, Zhangping Zuo, Peiyao Xu, Peiliu Yuan, Haozhi Bhave, Madhura Wei, Xiangying Yang, Ziyan Han, Lu Schmid, Sandra L Chen, Zhiming |
| author_facet | He, Zhangping Zuo, Peiyao Xu, Peiliu Yuan, Haozhi Bhave, Madhura Wei, Xiangying Yang, Ziyan Han, Lu Schmid, Sandra L Chen, Zhiming He, Zhangping Zuo, Peiyao Xu, Peiliu Yuan, Haozhi Bhave, Madhura Wei, Xiangying Yang, Ziyan Han, Lu Schmid, Sandra L Chen, Zhiming |
| collection | PubMed - marine biology |
| 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. |
| format | Artículo científico |
| id | pubmed_40424130 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Proceedings of the National Academy of Sciences of the United States of America |
| record_format | pubmed |
| spellingShingle | 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 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. |
| title | Dynamic early recruitment of GAK-Hsc70 regulates coated pit maturation. |
| topic | HSC70 Heat-Shock Proteins Endocytosis Humans Coated Pits, Cell-Membrane Clathrin Clathrin-Coated Vesicles Animals Intracellular Signaling Peptides and Proteins |
| url | https://pubmed.ncbi.nlm.nih.gov/40424130/ |