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

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 reesta

SUBMITTER: Dias MV 

PROVIDER: S-EPMC5103360 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature