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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

PRNP/prion protein regulates the secretion of exosomes modulating CAV1/caveolin-1-suppressed autophagy

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Author(s):
Dias, Marcos V. S. ; Teixeira, Bianca L. ; Rodrigues, Bruna R. ; Sinigaglia-Coimbra, Rita ; Porto-Carreiro, Isabel ; Roffe, Martin ; Hajj, Glaucia N. M. ; Martins, Vilma R.
Total Authors: 8
Document type: Journal article
Source: AUTOPHAGY; v. 12, n. 11, p. 2113-2128, 2016.
Web of Science Citations: 15
Abstract

Prion protein modulates many cellular functions including the secretion of trophic factors by astrocytes. Some of these factors are found in exosomes, which are formed within multivesicular bodies (MVBs) and secreted into the extracellular space to modulate cell-cell communication. The mechanisms underlying exosome biogenesis were not completely deciphered. Here, we demonstrate that primary cultures of astrocytes and fibroblasts from prnp-null mice secreted lower levels of exosomes than wild-type cells. Furthermore, prnp-null astrocytes exhibited reduced MVB formation and increased autophagosome formation. The reconstitution of PRNP expression at the cell membrane restored exosome secretion in PRNP-deficient astrocytes, whereas macroautophagy/autophagy inhibition via BECN1 depletion reestablished exosome release in these cells. Moreover, the PRNP octapeptide repeat domain was necessary to promote exosome secretion and to impair the formation of the CAV1-dependent ATG12-ATG5 cytoplasmic complex that drives autophagosome formation. Accordingly, higher levels of CAV1 were found in lipid raft domains instead of in the cytoplasm in prnp-null cells. Collectively, these findings demonstrate that PRNP supports CAV1-suppressed autophagy to protect MVBs from sequestration into phagophores, thus facilitating exosome secretion. (AU)

FAPESP's process: 12/19019-0 - Regulation of STAT3 activity and the role of secreted STI1/Hop protein in glioblastoma multiforme
Grantee:Bruna Roz Rodrigues
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 10/19200-1 - Identification of mechanisms of protein STI1/Hop secretion
Grantee:Marcos Vinicios Salles Dias
Support Opportunities: Scholarships in Brazil - Post-Doctoral
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