Dynamin 1xA interacts with Endophilin A1 via its spliced long C-terminus for ultrafast endocytosis.

Autor:	Imoto Y; Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA., Xue J; Cell Signalling Unit, Children's Medical Research Institute, The University of Sydney, Locked Bag 23, Wentworthville, 2145, NSW, Australia., Luo L; Institute for Molecular Bioscience, Institute for Molecular Bioscience Centre for Inflammation and Disease Research, and Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, 4072, Australia., Raychaudhuri S; Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Itoh K; Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA., Ma Y; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA., Craft GE; Cell Signalling Unit, Children's Medical Research Institute, The University of Sydney, Locked Bag 23, Wentworthville, 2145, NSW, Australia., Kwan AH; School of Life and Environmental Sciences and Sydney Nano Institute, University of Sydney, Camperdown, NSW, Australia., Ogunmowo TH; Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Ho A; Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Mackay JP; School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW, 2006, Australia., Ha T; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.; Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, Baltimore, MD, USA.; Howard Hughes Medical Institute, Baltimore, MD, USA., Watanabe S; Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. shigeki.watanabe@jhmi.edu.; The Center for Cell Dynamics, Johns Hopkins University, Baltimore, MD, USA. shigeki.watanabe@jhmi.edu.; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, MD, USA. shigeki.watanabe@jhmi.edu., Robinson PJ; Cell Signalling Unit, Children's Medical Research Institute, The University of Sydney, Locked Bag 23, Wentworthville, 2145, NSW, Australia. probinson@cmri.org.au.
Jazyk:	angličtina
Zdroj:	The EMBO journal [EMBO J] 2024 Aug; Vol. 43 (16), pp. 3327-3357. Date of Electronic Publication: 2024 Jun 21.
DOI:	10.1038/s44318-024-00145-x
Abstrakt:	Dynamin 1 mediates fission of endocytic synaptic vesicles in the brain and has two major splice variants, Dyn1xA and Dyn1xB, which are nearly identical apart from the extended C-terminal region of Dyn1xA. Despite a similar set of binding partners, only Dyn1xA is enriched at endocytic zones and accelerates vesicle fission during ultrafast endocytosis. Here, we report that Dyn1xA achieves this localization by preferentially binding to Endophilin A1 through a newly defined binding site within its long C-terminal tail extension. Endophilin A1 binds this site at higher affinity than the previously reported site, and the affinity is determined by amino acids within the Dyn1xA tail but outside the binding site. This interaction is regulated by the phosphorylation state of two serine residues specific to the Dyn1xA variant. Dyn1xA and Endophilin A1 colocalize in patches near the active zone, and mutations disrupting Endophilin A binding to the long tail cause Dyn1xA mislocalization and stalled endocytic pits on the plasma membrane during ultrafast endocytosis. Together, these data suggest that the specificity for ultrafast endocytosis is defined by the phosphorylation-regulated interaction of Endophilin A1 with the C-terminal extension of Dyn1xA. (© 2024. The Author(s).)
Databáze:	MEDLINE
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