scholarly journals Itraconazole inhibits nuclear delivery of extracellular vesicle cargo by disrupting the entry of late endosomes into the nucleoplasmic reticulum

2021 ◽  
Vol 10 (10) ◽  
Author(s):  
Mark F. Santos ◽  
Germana Rappa ◽  
Jana Karbanová ◽  
Simona Fontana ◽  
Maria Antonietta Di Bella ◽  
...  

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1096 ◽  
Author(s):  
Guerra ◽  
Bucci

RAB7 is a small guanosine triphosphatase (GTPase) extensively studied as regulator of vesicular trafficking. Indeed, its role is fundamental in several steps of the late endocytic pathway, including endosome maturation, transport from early endosomes to late endosomes and lysosomes, clustering and fusion of late endosomes and lysosomes in the perinuclear region and lysosomal biogenesis. Besides endocytosis, RAB7 is important for a number of other cellular processes among which, autophagy, apoptosis, signaling, and cell migration. Given the importance of RAB7 in these cellular processes, the interest to study the role of RAB7 in cancer progression is widely grown. Here, we describe the current understanding of oncogenic and oncosuppressor functions of RAB7 analyzing cellular context and other environmental factors in which it elicits pro and/or antitumorigenic effects. We also discuss the role of RAB7 in cisplatin resistance associated with its ability to regulate the late endosomal pathway, lysosomal biogenesis and extracellular vesicle secretion. Finally, we examined the potential cancer therapeutic strategies targeting the different molecular events in which RAB7 is involved.



Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1931 ◽  
Author(s):  
Denis Corbeil ◽  
Mark F. Santos ◽  
Jana Karbanová ◽  
Thomas Kurth ◽  
Germana Rappa ◽  
...  

Extracellular membrane vesicles (EVs) are emerging as new vehicles in intercellular communication, but how the biological information contained in EVs is shared between cells remains elusive. Several mechanisms have been described to explain their release from donor cells and the initial step of their uptake by recipient cells, which triggers a cellular response. Yet, the intracellular routes and subcellular fate of EV content upon internalization remain poorly characterized. This is particularly true for EV-associated proteins and nucleic acids that shuttle to the nucleus of host cells. In this review, we will describe and discuss the release of EVs from donor cells, their uptake by recipient cells, and the fate of their cargoes, focusing on a novel intracellular route wherein small GTPase Rab7+ late endosomes containing endocytosed EVs enter into nuclear envelope invaginations and deliver their cargo components to the nucleoplasm of recipient cells. A tripartite protein complex composed of (VAMP)-associated protein A (VAP-A), oxysterol-binding protein (OSBP)-related protein-3 (ORP3), and Rab7 is essential for the transfer of EV-derived components to the nuclear compartment by orchestrating the particular localization of late endosomes in the nucleoplasmic reticulum.



2018 ◽  
Vol 293 (36) ◽  
pp. 13834-13848 ◽  
Author(s):  
Mark F. Santos ◽  
Germana Rappa ◽  
Jana Karbanová ◽  
Thomas Kurth ◽  
Denis Corbeil ◽  
...  


Oncotarget ◽  
2017 ◽  
Vol 8 (9) ◽  
pp. 14443-14461 ◽  
Author(s):  
Germana Rappa ◽  
Mark F. Santos ◽  
Toni M. Green ◽  
Jana Karbanová ◽  
Justin Hassler ◽  
...  


2019 ◽  
Author(s):  
S. Kohli ◽  
P. Markmeyer ◽  
F. Lochmann ◽  
M.M. Al-Dabet ◽  
S. Ranjan ◽  
...  




2015 ◽  
Vol 6 (3-4) ◽  
pp. 157-161
Author(s):  
Federica Vannini ◽  
Francesco Russo


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