Biology Reference
In-Depth Information
a
-Arrestins and visual/
b
-arrestins share another trait required to trigger
endocytosis of their cargo, a dephosphorylation step. The bulk (70%) of
b
-arrestin is cytosolic, phosphorylated, and “inactive.” To bind an activated
GPCR, they are dephosphorylated at the PM. Once the receptor is inter-
nalized,
b
-arrestins can be rephosphorylated on the endosome.
59-62
Visual
arrestin is phosphorylated upon light activation
63
and its dephosphorylation
is required for the arrestin-clathrin interaction to proceed.
64
Inactive, phos-
phorylated Rod1/ART4 is mostly cytosolic and shielded by an interaction
with 14-3-3. Its activation releases 14-3-3 and allows its dephosphorylation
by PP1 phosphatase and its subsequent ubiquitination by Rsp5.
85
Upon acti-
vation, Ldb9(Cvs7)/ART1, but not Rod1/ART4, redistributes at the PM
and their cargoes (Can1, Jen1) are endocytosed.
10,85
The example of PalF
introduces some degree of complexity, as this paralogue of Rim8/ART9
in
Aspergillus
is phosphorylated and ubiquitinated in a signal-dependent
manner before interacting with the signal sensor PalH.
87
A clue to understanding the degradation mechanism of the cargoes
comes from the demonstration that most ARRDCs interact with subunits
of the ESCRT machinery.
79
The ESCRT complex is the sorting machinery
scaffolded at the membrane of the multivesicular body (MVB) that recog-
nizes and sorts cargoes destined for degradation by their ubiquitin label
and generates intraluminal vesicles enriched with cargoes. After fusion of
the MVB with lysosomes, these intraluminal vesicles are degraded by the
lysosomal lytic enzymes.
147-149
ARTs or ARRDCs interact with ESCRT
subunits not only at the endosome but also at the PM, as shown for the fun-
gal signaling complex with PalF/Rim8
150
and with diverse ARRDCs in the
budding process of viruses.
79
Recent results with the
b
2
-adrenergic receptor
shed new light on the choice between recycling and degradation pathways.
As discussed above, the class A
b
2
-adrenergic receptor normally recruits
b
-arrestin 2 upon activation and is only transiently downregulated.
151
This same receptor interacts also with ARRDC3 as the initial step of its
ubiquitin-dependent degradation in the lysosome.
82
Interaction with
ESCRT-0 has also been demonstrated for
b
-arrestin 1 in the degradation
pathway of CXCR4.
28
If the choice between alternate interactors (arrestins
or ARRDCs) is verified for other receptors and the full repertoire of
a
-/
b
-
arrestins, it would provide a means to control the diversity of the followed
itineraries, toward either recycling or degradation.
Apart from the involvement of both protein subfamilies in the trafficking
of membrane-embedded receptors, the functional similarities between
VPS26 and the
a
-/
b
-arrestins are rather weak. Despite its arrestin fold
Search WWH ::
Custom Search