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Molecular Mechanisms of Exosome Secr...

Liu, Di-Ao,

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Molecular Mechanisms of Exosome Secretion /

Record Type:	Electronic resources : Monograph/item
Title/Author:	Molecular Mechanisms of Exosome Secretion // Di-Ao Liu.
Author:	Liu, Di-Ao,
Description:	1 electronic resource (190 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
Contained By:	Dissertations Abstracts International85-12B.
Subject:	Biology. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30992944
ISBN:	9798382831008

Molecular Mechanisms of Exosome Secretion /
Liu, Di-Ao,

Molecular Mechanisms of Exosome Secretion /Di-Ao Liu. - 1 electronic resource (190 pages)

Source: Dissertations Abstracts International, Volume: 85-12, Section: B.

Exosomes are small (30-150 nm) extracellular vesicles (EVs) that obtain their membrane through the inward invagination of the endosomes, which are known as multivesicular endosomes (MVEs). Exosomes are secreted to the extracellular milieu when MVEs dock and fuse with the plasma membrane. However, MVEs can also fuse with lysosomes for degradation. How MVEs are directed to the plasma membrane rather than to lysosomes is unclear. My thesis work mainly focused on the molecular mechanisms that control the exocytic trafficking of MVEs and, ultimately, exosome secretion. We found that the conversion of phosphatidylinositol-3-phosphate (PI(3)P) to phosphatidylinositol-4-phosphate (PI(4)P) catalyzed by Myotubularin 1 (MTM1) and phosphatidylinositol 4-kinase type IIα (PI4KIIα) on the surface of MVEs mediates the recruitment of the exocyst complex. The exocyst then targets the MVEs to the plasma membrane for exosome secretion. Disrupting PI(4)P generation or exocyst function blocked exosomal secretion of Programmed death-ligand 1 (PD-L1), a key immune checkpoint protein in tumor cells, and led to its accumulation in lysosomes.In collaboration with the lab members, we also found that cells respond to extracellular matrix (ECM) stiffness for exosome secretion. Increased ECM stiffness activates Akt, which directly phosphorylates Rabin8 and promotes its guanine nucleotide exchange activity toward Rab8 for the exocytic trafficking of MVEs and exosome secretion. Together, my work suggests that exocytic trafficking of MVEs and exosome secretion is mediated by phospholipids, Rab GTPases, and the exocyst complex, which is regulated by signaling molecules in response to extracellular cues.

English

ISBN: 9798382831008Subjects--Topical Terms:

522710
Biology.
Subjects--Index Terms:

Extracellular vesicles

Molecular Mechanisms of Exosome Secretion /
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520 $a Exosomes are small (30-150 nm) extracellular vesicles (EVs) that obtain their membrane through the inward invagination of the endosomes, which are known as multivesicular endosomes (MVEs). Exosomes are secreted to the extracellular milieu when MVEs dock and fuse with the plasma membrane. However, MVEs can also fuse with lysosomes for degradation. How MVEs are directed to the plasma membrane rather than to lysosomes is unclear. My thesis work mainly focused on the molecular mechanisms that control the exocytic trafficking of MVEs and, ultimately, exosome secretion. We found that the conversion of phosphatidylinositol-3-phosphate (PI(3)P) to phosphatidylinositol-4-phosphate (PI(4)P) catalyzed by Myotubularin 1 (MTM1) and phosphatidylinositol 4-kinase type IIα (PI4KIIα) on the surface of MVEs mediates the recruitment of the exocyst complex. The exocyst then targets the MVEs to the plasma membrane for exosome secretion. Disrupting PI(4)P generation or exocyst function blocked exosomal secretion of Programmed death-ligand 1 (PD-L1), a key immune checkpoint protein in tumor cells, and led to its accumulation in lysosomes.In collaboration with the lab members, we also found that cells respond to extracellular matrix (ECM) stiffness for exosome secretion. Increased ECM stiffness activates Akt, which directly phosphorylates Rabin8 and promotes its guanine nucleotide exchange activity toward Rab8 for the exocytic trafficking of MVEs and exosome secretion. Together, my work suggests that exocytic trafficking of MVEs and exosome secretion is mediated by phospholipids, Rab GTPases, and the exocyst complex, which is regulated by signaling molecules in response to extracellular cues.
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650 4 $a Cellular biology. $3 3172791
650 4 $a Molecular biology. $3 517296
650 4 $a Immunology. $3 611031
653 $a Extracellular vesicles
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653 $a Tumor cells
653 $a Extracellular matrix
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