Another adaptor: Ran binding protein 9 and 10

Ran binding protein 9 and 10 (RanBP9/10) may act as adaptor protein with modulatory roles on signalling initiated by Gq-coupled receptors favourably in multimeric forms.

Some GPCRs can couple to different G-proteins accordingly to their organisation or arrangement at the membrane. For instance, different heterodimerisation of dopamine receptors, D2 with either D1 or D5 could result in an alternative coupling to Gq as have been documented (reviewed by Hasbi et al 2010). The D1-D2 heteromer could induce rapid, transient calcium signal via Gq, PLC, PKC and IP3R (Lee et al. 2004; Rashid et al. 2007), whereas the signal generation by the D2-D5 heteromers might involve more intricate regulations possibly at the level of receptor conformational changes induced by agonist binding.

Rex et al. has shown that D1 receptor can interact with multifunctional adaptor proteins known as Ran binding protein 9 and 10 (RanBP9/10), which were also shown to interact with PKC gamma and delta isoforms; the interactions result in up-regulation of D1 phosphorylation at its basal level. Interestingly, overexpression of RanBPs resulted in decreased cAMP accumulation in response to dopamine stimulation by about 45%, whilst the potency was statistically unaffected. When the effect of D1 expression was determined by saturation binding, RanBP10 was shown not to affect D1 expression; however, RanBP9 almost halved the D1 binding (Rex et al. 2010).

RanBP9/10 have been reported to involve in cellular actions such as microtubule spindle assembly (Schulze et al. 2007) and myofibrillogenesis (Bowman et al 2008). RanBP9 was also shown to associate with receptor tyrosine kinase, hepatocyte growth factor receptor MET, initiating Ras/ERK pathway (Wang et al. 2002).             


The links to uniprot:

Ran binding protein 9

Ran binding protein 10


Bibliography

Bowman AL et al 2008. The Rho-Guanine Nucleotide Exchange Factor Domain of Obscurin Regulates Assembly of Titin at the Z-Disk through Interactions with Ran Binding Protein 9. Mol Bio Cell 19: 3782-92.

Hasbi A, O’Dowd BF & George SR. 2010. Heteromerization of dopamine D2 receptors with dopamine D1 or D5 receptors generates intracellular calcium signaling by different mechanisms. Curr Opin Pharmacol. 10(1): 93. doi:10.1016/j.coph.2009.09.011.

Lee SP, So CH, Rashid AJ, Varghese G, Cheng R, Lanca AJ, O’Dowd BF, George SR. Dopamine D1 and D2 receptor co-activation generates a novel phospholipase C-mediated calcium signal. J Biol Chem 2004;279:35671–35678.

Rashid AJ, So CH, Kong MM, Furtak T, El-Ghundi M, Cheng R, O'Dowd BF, George SR. D1–D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/ 11 in the striatum. Proc Natl Acad Sci USA 2007;104:654–659.

Rex EB et al. 2010. Identification of RanBP 9/10 as Interacting Partners for Protein Kinase C (PKC)γ/δ and the D1 Dopamine Receptor: Regulation of PKC-Mediated Receptor Phosphorylation. Mol Phamacol 78: 69-80.

Schulze H et al. 2007. RanBP10 Is a Cytoplasmic Guanine Nucleotide Exchange
Factor That Modulates Noncentrosomal Microtubules. J Bio Chem 283: 14109–14119.

Wang D et al. 2002. Activation of Ras/Erk Pathway by a Novel MET-interacting Protein RanBPM. J Biol Chem 2277: 36216-22.