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In human melanoma cells, by contrast, the depletion of neutral sphingomyelinases impairs
neitherMVB biogenesis (Van Niel et al. 2011) nor exosome secretion (G. Van Niel & G. Raposo,
unpublished data); instead, a CD63-dependent mechanism is required for ILV/exosome formation.
CD63 is instrumental in targeting the EBV-encoded LMP1 protein to ILVs and allowing
its subsequent release in exosomes (Verweij et al. 2011). In HEK293 cells, CD9 or CD82 (but
not CD63) overexpression was shown to induce secretion of β-catenin by exosomes, which were
still generated through a ceramide-dependent mechanism (Chairoungdua et al. 2010). In a rat
pancreatic adenocarcinoma cell line, expression of the tetraspanin Tspan8 led to modifications in
the exosome content in mRNA and transmembrane proteins (VCAM-1, α4 integrin) (Nazarenko
et al. 2010). CD81-enriched domains have been proposed recently as sorting platforms for exosomal
proteins (Perez-Hernandez et al. 2013) and may certainly account for ESCRT-independent
sorting of some cargoes and the formation of a population of ILVs: Proteins that are known to
interact with certain tetraspanins were found in exosomes via mass spectrometry, and in CD81-
deficient animals, exosomes were found to be devoid of CD81-interacting molecules, which are
normally loaded onto exosomes.
Finally, a small integral membrane protein of lysosomes and late endosomes, called SIMPLE,
was recently shown to be secreted in association with exosomes, and fibroblasts expressing its
mutant form found in Charcot-Marie-Tooth disease patients, CMT1C, secreted less CD63- and
ALIX-containing exosomes, whereas flotillin secretion was unaffected (Zhu et al. 2013). How
SIMPLE regulates exosome secretion, and whether it is through binding to TSG101 or to Nedd4
type-3 ubiquitin ligase, two proteins for which SIMPLE contains a binding domain, was not
elucidated in this study. The latter interaction is potentially relevant to exosome biogenesis and
secretion, because a transmembrane protein able to bindNedd4, Nedd-family interacting protein
1, has been shown to promote exosome secretion and targeting of cytosolic proteins, such as the
PTEN tumor suppressor, into these exosomes (Putz et al. 2012).
有没有人看过这一段话,是什么意思呢?跟楼主所说的4有没有关系呢?求指点 |
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