Regulation of Post-Golgi Traffic of G Protein-Coupled Receptors - GPCR Signalling Complexes: Synthesis, Assembly, Trafficking and Specificity - page 87

receptor 1B, and the nucleotide receptors (P2Y 1 R, P2Y 2 R, P2Y 4 R, and P2Y 11 R)
(Luo et al. 2011 ). In addition to p24, p23, another member of the p24 family protein,
is also able to bind to these GPCRs. More interestingly, the conserved acidic resi-
dues located in the second extracellular loop are required for the interaction of
P2Y 4 R and P2Y 11 R with p24 (Luo et al. 2011 ). These data strongly imply that
GPCRs, via the acidic domains, may interact with Golgi-localized proteins, such as
the p24 family proteins p23 and p24, to modulate their post-Golgi trafficking along
the biosynthetic pathway.

5.3.5 The YS Motif in Post-Golgi Traf fi c of a 2 -AR

As described above the C-termini of GPCRs contain signals directing the post-
Golgi transport of GPCRs and their function can be mediated by physically
associating with components of the transport machinery, such as small GTPases.
Similar to the C-termini, the N-termini are also involved in the regulation of
anterograde trafficking of newly synthesized GPCRs. For example, the deletion
of the N-termini facilitated the cell-surface export of a 1D -AR and a 2C -AR,
suggesting that the N-termini may contain signals retaining the receptors in the
ER (Angelotti et al. 2010 ; Hague et al. 2004 ). Indeed, a hydrophobic sequence
in the C-terminus of a 2C -AR was proven to function as an ER retention motif
(Angelotti et al. 2010 ), which provides a mechanism responsible for the intra-
cellular accumulation of a 2C -AR in some types of cells.
We have found that the N-termini may play an important role in dictating GPCR
export from the Golgi. We have demonstrated that single and double substitution of
Y12 and S13 residues in the membrane-proximal N-terminal region significantly
reduced the cell-surface expression of a 2B -AR (Dong and Wu 2006 ) and the Y12/
S13 motif mutants were retained in the Golgi apparatus (Dong and Wu 2006 ) . These
data suggest that the Y12/S13 motif mediates a 2B -AR export at the level of the
Golgi. The YS motif only exists in three a 2 -AR family members (Dong and Wu
2006 ) (Fig. 5.2 ) and indeed, it exerts a similar function on a 2A -AR traf fi cking (Dong
and Wu 2006 ). Therefore, the YS motif may function as an export signal specifically
modulating the Golgi export of the members of a 2 -AR subfamily. It should be
pointed out that the N-terminal tails are positioned towards the lumen of the ER and

NT

α 2A -AR

Human GARATP YS LQ

Rat GTRATP YS LQ

Mouse GTRATP YS LQ

α 2B -AR

Human MDHQDP YS VQ

Rat MDHQEP YS VQ

Mouse MVHQEP YS VQ

Fig. 5.2 The conserved YS
motif in the N-termini (NT)
of three a 2 -AR subtypes

α 2C -AR

Human GPPRGQ YS AG

Rat GPPPGQ YS AG

Mouse VPPPGQ YS AG