The unconventional secretion of stress-inducible protein 1 by a heterogeneous population of extracellular vesicles


Autoria(s): Hajj, Glaucia N. M.; Arantes, Camila P.; Dias, Marcos Vinicios Salles; Roffé, Martín; Costa-Silva, Bruno; Lopes, Marilene Hohmuth; Porto-Carreiro, Isabel; Rabachini, Tatiana; Lima, Flávia R.; Beraldo, Flávio H.; Prado, Marco M. A.; Linden, Rafael; Martins, Vilma R.
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

23/04/2014

23/04/2014

01/09/2013

Resumo

The co-chaperone stress-inducible protein 1 (STI1) is released by astrocytes, and has important neurotrophic properties upon binding to prion protein (PrPC). However, STI1 lacks a signal peptide and pharmacological approaches pointed that it does not follow a classical secretion mechanism. Ultracentrifugation, size exclusion chromatography, electron microscopy, vesicle labeling, and particle tracking analysis were used to identify three major types of extracellular vesicles (EVs) released from astrocytes with sizes ranging from 20–50, 100–200, and 300–400 nm. These EVs carry STI1 and present many exosomal markers, even though only a subpopulation had the typical exosomal morphology. The only protein, from those evaluated here, present exclusively in vesicles that have exosomal morphology was PrPC. STI1 partially co-localized with Rab5 and Rab7 in endosomal compartments, and a dominant-negative for vacuolar protein sorting 4A (VPS4A), required for formation of multivesicular bodies (MVBs), impaired EV and STI1 release. Flow cytometry and PK digestion demonstrated that STI1 localized to the outer leaflet of EVs, and its association with EVs greatly increased STI1 activity upon PrPC-dependent neuronal signaling. These results indicate that astrocytes secrete a diverse population of EVs derived from MVBs that contain STI1 and suggest that the interaction between EVs and neuronal surface components enhances STI1–PrPC signaling

FAPESP, 2009/14027-2

FAPESP, 2012/04370-4

PrioNet-Canada, Canadian Institutes of Health Research (CIHR)

Canadian Foundation for Innovation and Ontario Research Fund

CNPq

FAPERJ

Identificador

Cellular and Molecular Life Sciences, Basel, v.70, n.17, p.3211-3227, 2013

http://www.producao.usp.br/handle/BDPI/44619

10.1007/s00018-013-1328-y

http://dx.doi.org/10.1007/s00018-013-1328-y

Idioma(s)

eng

Publicador

Birkhauser

Basel

Relação

Cellular and Molecular Life Sciences

Direitos

restrictedAccess

Springer Basel

Palavras-Chave #Exosomes #Chaperones #Prion protein #STI1 #Extracellular vesicles #Vesículas extracelulares #PROTEÍNAS #ESTRESSE
Tipo

article

original article

publishedVersion