Regulation of Post-Golgi Traffic of G Protein-Coupled Receptors - GPCR Signalling Complexes: Synthesis, Assembly, Trafficking and Specificity - page 86

motif is clearly linked to the pathogenesis of neurodegenerative diseases, particularly
the severe forms such as autosomal dominant retinitis pigmentosa. The function of
the VxPx motif in regulating rhodopsin trafficking has been suggested to be
mediated through interacting with Tctex-1, a light chain of cytoplasmic dynein that
translocates rhodopsin-bearing vesicles along microtubules (Tai et al. 1999 ) .
Deretic et al . have demonstrated that the VxPx motif mediates rhodopsin
interaction with the small GTPase ARF4 (Deretic et al. 2005 ) and this interaction
plays an important role in receptor sorting at the TGN into membrane carriers which
transport to the rod outer segments (Deretic et al. 2005 ; Mazelova et al. 2009 ) . They
have also identified a complex containing ARF4 that is formed on the TGN and
regulates post-Golgi transport of rhodopsin (Mazelova et al. 2009 ) . These studies
have demonstrated that the C-terminal sequence through physically association
with transport machinery proteins may provide an efficient transport system for the
vectorial delivery of large numbers of nascent rhodopsin. In addition, mutation of
the glutamic acid residue at the position 150 in the second intracellular loop of
rhodopsin (E150K) induced an accumulation of the receptor in the cis/medial Golgi
compartments and this mutation is linked to the development of autosomal recessive
retinitis pigmentosa (Zhu et al. 2006 ), further suggesting that rhodopsin export from
the Golgi and subsequent transport to the functional destination is a regulated pro-
cess. These data also suggest that defective post-Golgi traffic may be the molecular
basis of retinitis pigmentosa.

5.3.4 The Acidic Motifs and Their Interaction with the p24

Family Proteins in the Post-Golgi Transport of GPCRs

The di-acidic sequences have been demonstrated to function as ER export motifs
in several membrane proteins (Sevier et al. 2000 ; Ma et al. 2001 ; Nishimura and
Balch 1997 ; Nishimura et al. 1999 ; Zuzarte et al. 2007 ; Wang et al. 2004 ) . Their
ER export functions are mediated through directly interacting with Sec24, a com-
ponent of ER-derived COPII vesicles that mediate cargo transport exclusively from
the ER. This interaction enhances the recruitment and concentration of the cargo
carrying the di-acidic motifs into the COPII vesicles. The di-acidic motifs in the
membrane-proximal C-termini have been also demonstrated to regulate the trans-
port of AT1R and AT2R, but not b 2 -AR and a 1B -AR, from the ER (Zhang et al.
2011 ). In addition to regulating ER export, the di-acidic motifs are also involved in
post-Golgi trafficking through interacting with the adaptor protein AP3 (Nishimura
et al. 2002 ) .
Luo et al. have demonstrated that protease-activated receptor-2 (PAR2) inter-
acted with p24A, a type 1 transmembrane protein. This interaction is regulated by
the small GTPase ARF1 and plays an important role in the transport of PAR-2 from
the Golgi to the plasma membrane (Luo et al. 2007 ). Subsequently, this group dem-
onstrates that p24 interacted with several other GPCRs, including PAR-1, m -opioid