title: From cradle to twilight: the carboxyl terminus directs the fate of the A(2A)-adenosine receptor.
abstract: The extended carboxyl terminus of the A(2A)-adenosine receptor is known to engage several proteins other than those canonically involved in signalling by GPCRs (i.e., G proteins, G protein-coupled receptor kinases/GRKs, arrestins). The list includes the deubiquinating enzyme USP4, α-actinin, the guanine nucleotide exchange factor for ARF6 ARNO, translin-X-associated protein, calmodulin, the neuronal calcium binding protein NECAB2 and the synapse associated protein SAP102. However, if the fate of the A(2A)-receptor is taken into account - from its birthplace in the endoplasmic reticulum to its presumed site of disposal in the lysosome, it is evident that many more proteins must interact with the A(2A)-adenosine receptor. There are several arguments that support the conjecture that these interactions will preferentially occur with the carboxyl terminus of the A(2A)-adeonsine receptor: (i) the extended carboxyl terminus (of 122 residues=) offers the required space to accommodate companions; (ii) analogies can be drawn with other receptors, which engage several of these binding partners with their C-termini. This approach allows for defining the nature of the unknown territory. As an example, we posit a chaperone/coat protein complex-II (COPII) exchange model that must occur on the carboxyl terminus of the receptor. This model accounts for the observation that a minimum size of the C-terminus is required for correct folding of the receptor. It also precludes premature recruitment of the COPII-coat to a partially folded receptor.
authors.affiliation: Institute of Pharmacology, Medical University of Vienna, Austria.
authors.forename: Simon
authors.initials: S
authors.lastname: Keuerleber
authors.forename: Ingrid
authors.initials: I
authors.lastname: Gsandtner
authors.forename: Michael
authors.initials: M
authors.lastname: Freissmuth
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D043705:Receptor, Adenosine A2A