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Mast cell secretory granule fusion with amphisomes coordinates their homotypic fusion and release of exosomes.
Omari, Sewar; Roded, Amit; Eisenberg, Maggie; Ali, Hydar; Fukuda, Mitsunori; Galli, Stephen J; Sagi-Eisenberg, Ronit.
Afiliación
  • Omari S; Department of Cell and Developmental Biology, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
  • Roded A; Department of Cell and Developmental Biology, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
  • Eisenberg M; Department of Cell and Developmental Biology, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
  • Ali H; Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Fukuda M; Laboratory of Membrane Trafficking Mechanisms, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Aobayama, Aoba-ku, Sendai, Miyagi 980-8578, Japan.
  • Galli SJ; Departments of Pathology and of Microbiology and Immunology, and Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA 94305-5176, USA.
  • Sagi-Eisenberg R; Department of Cell and Developmental Biology, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 69978, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel. Electronic address: histol3@tauex.tau.ac.il.
Cell Rep ; 43(7): 114482, 2024 Jul 23.
Article en En | MEDLINE | ID: mdl-38985670
ABSTRACT
Secretory granule (SG) fusion is an intermediate step in SG biogenesis. However, the precise mechanism of this process is not completely understood. We show that Golgi-derived mast cell (MC) SGs enlarge through a mechanism that is dependent on phosphoinositide (PI) remodeling and fusion with LC3+ late endosomes (amphisomes), which serve as hubs for the fusion of multiple individual SGs. Amphisome formation is regulated by the tyrosine phosphatase PTPN9, while the subsequent SG fusion event is additionally regulated by the tetraspanin protein CD63 and by PI4K. We also demonstrate that fusion with amphisomes imparts to SGs their capacity of regulated release of exosomes. Finally, we show that conversion of PI(3,4,5)P3 to PI(4,5)P2 and the subsequent recruitment of dynamin stimulate SG fission. Our data unveil a key role for lipid-regulated interactions with the endocytic and autophagic systems in controlling the size and number of SGs and their capacity to release exosomes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vesículas Secretoras / Exosomas / Mastocitos Límite: Animals Idioma: En Revista: Cell Rep Año: 2024 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vesículas Secretoras / Exosomas / Mastocitos Límite: Animals Idioma: En Revista: Cell Rep Año: 2024 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Estados Unidos