Chunk #28 — RESULTS — Differential expression of signaling proteins in calcium, cyclic nucleotide and small GTPase 2nd messenger pathways in PCPs — Adenylyl cyclase, phosphodiesterase and cAMP signaling
In mediating GPCR signaling, the synthesis, degradation and spatiotemporal dynamics of cAMP are stringently regulated at each step (Halls and Cooper, 2011). We found that, while the G protein subunits themselves are broadly expressed, regulators of G protein signaling (RGS) family members manifest highly differential expression, often with binary-ON/OFF patterns among PCPs (AUROC=0.93; Figure 5A–C); this suggests that the turning-off of Gα subunit, a crucial step of G protein regulation, is implemented in a cell-type specific manner. Downstream to G proteins, 7 of the 9 adenylate cyclase (ACs) members with different catalytic and regulatory properties are differentially expressed (AUROC=0.85; Figure 5A–C). More strikingly, phosphodiesterases (PDEs), which mediate rapid cAMP degradation (Maurice et al., 2014), is among the top differentially expressed gene families (AUROC=0.94): 15 of the 22 members are differentially expressed, often with ON/OFF patterns (Figure 5A–C, Figure S5A). The specific and correlated transcription of AC, PDE and their functional effectors in PCPs suggest possible mechanisms that craft the spatiotemporal patterns of a ubiquitous 2nd messenger to direct cell and receptor (i.e. input) specific signal transduction, in part through subcellular targeted “signalosomes” containing particular members of synthetic and degradation enzymes with distinct catalytic and regulatory properties.
