Abstract:
:Because small-molecule activators of adenylyl cyclases (AC) affect ACs cell-wide, it is challenging to explore the signaling consequences of AC activity emanating from specific intracellular compartments. We explored this issue using a series of engineered, optogenetic, spatially restricted, photoactivable adenylyl cyclases (PACs) positioned at the plasma membrane (PM), the outer mitochondrial membrane (OMM), and the nucleus (Nu). The biochemical consequences of brief photostimulation of PAC is primarily limited to the intracellular site occupied by the PAC. By contrast, sustained photostimulation results in distal cAMP signaling. Prolonged cAMP generation at the OMM profoundly stimulates nuclear protein kinase (PKA) activity. We have found that phosphodiesterases 3 (OMM and PM) and 4 (PM) modulate proximal (local) cAMP-triggered activity, whereas phosphodiesterase 4 regulates distal cAMP activity as well as the migration of PKA's catalytic subunit into the nucleus.
journal_name
Cell Chem Bioljournal_title
Cell chemical biologyauthors
O'Banion CP,Vickerman BM,Haar L,Lawrence DSdoi
10.1016/j.chembiol.2019.07.004subject
Has Abstractpub_date
2019-10-17 00:00:00pages
1393-1406.e7issue
10eissn
2451-9456issn
2451-9448pii
S2451-9456(19)30216-8journal_volume
26pub_type
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