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

Author(s):Show less -

Hajj, Glaucia N. M. ^{[1, 2, 3]} ; Arantes, Camila P. ^[4] ; Salles Dias, Marcos Vinicios ^{[1, 2, 3]} ; Roffe, Martin ^{[1, 2, 3]} ; Costa-Silva, Bruno ^{[1, 2, 3]} ; Lopes, Marilene H. ^[5] ; Porto-Carreiro, Isabel ^[6] ; Rabachini, Tatiana ^[7] ; Lima, Flavia R. ^[8] ; Beraldo, Flavio H. ^{[9, 10]} ; Prado, Marco M. A. ^{[9, 10]} ; Linden, Rafael ^[6] ; Martins, Vilma R. ^{[1, 2, 3]}

Affiliation

^[1] Natl Inst Translat Neurosci, Sao Paulo - Brazil

^[2] AC Camargo Hosp, Int Res Ctr, BR-01508010 Sao Paulo - Brazil

^[3] Natl Inst Oncogen, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Dept Biomed Sci, Sao Paulo - Brazil

^[6] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, BR-21941 Rio De Janeiro - Brazil

^[7] Ludwig Inst Canc Res, Sao Paulo - Brazil

^[8] Univ Fed Rio de Janeiro, Inst Ciencias Biomed, Rio De Janeiro - Brazil

^[9] Univ Western Ontario, Robarts Res Inst, Dept Anat & Cell Biol, London, ON - Canada

^[10] Univ Western Ontario, Robarts Res Inst, Dept Physiol & Pharmacol, London, ON - Canada

• Document type: Journal article
• Source: CELLULAR AND MOLECULAR LIFE SCIENCES; v. 70, n. 17, p. 3211-3227, SEP 2013.
• Web of Science Citations: 21

Abstract

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. (AU)

• FAPESP's process: 09/14027-2 - Mechanisms associated with the function of prion protein and its ligand STI1/Hop: therapeutic approaches
• Grantee: Vilma Regina Martins
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/04370-4 - Translational control in the nervous system: tumor mechanisms
• Grantee: Glaucia Noeli Maroso Hajj
• Support Opportunities: Regular Research Grants