Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.22.36 (
caspase-1
)
6,285
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Intracellular trafficking is a tightly regulated cellular process, mediated in part by Rab GTPases and their corresponding effector proteins. Viruses have evolved mechanisms to hijack these processes to promote their lifecycles. Here we describe a mechanism by which cleavage of the Rab7 adaptor protein,
RILP
(Rab interacting lysosomal protein) is induced by viral infection. We report that
RILP
is directly cleaved by
caspase-1
and we have identified a novel
caspase-1
recognition site at aspartic acid 75 within the
RILP
sequence. Alanine substitution at D75 blocks
caspase-1
-mediated
RILP
cleavage. Full-length
RILP
localizes in a tight vesicular structure near the perinuclear region while the cleaved form of
RILP
re-distributes throughout the cytoplasm. However, cleavage alone was insufficient to re-localize
RILP
to the cellular periphery and re-localization required specific phosphorylation events near the
caspase-1
recognition site. The combination of cleavage and phosphorylation were both needed for release from the dynein component p150
Glued
and redistribution of CD63
+ve
intracellular vesicles.
...
PMID:Caspase-1 regulates cellular trafficking via cleavage of the Rab7 adaptor protein RILP. 3010 68
Cells respond to inflammatory disease states by releasing exosomes containing highly specific protein and RNA cargos, but how inflammation alters cargo specificity and secretion of exosomes is unknown. We show that increases in exosome secretion induced by either viral infection or LPS/ATP exposure result from inflammasome activation and subsequent
caspase-1
-dependent cleavage of the trafficking adaptor protein
RILP
. This cleaved form of
RILP
promotes the movement of multivesicular bodies toward the cell periphery and induces selective exosomal miRNA cargo loading. We have identified a common short sequence motif present in miRNAs that are selectively loaded into exosomes after
RILP
cleavage. This motif binds the RNA binding protein FMR1 and directs miRNA loading into exosomes via interaction with components of the ESCRT (endosomal sorting complex required for transport) pathway. These results indicate that inflammasome-mediated
RILP
cleavage, and sequence-specific interactions between miRNAs and FMR1, play a significant role in exosome cargo loading and enhanced secretion during cellular inflammatory responses.
...
PMID:The RNA binding protein FMR1 controls selective exosomal miRNA cargo loading during inflammation. 3298 92
