Details

Autor(en) / Beteiligte

• Ostrom, Katrina F
• LaVigne, Justin E
• Brust, Tarsis F
• Seifert, Roland
• Dessauer, Carmen W
• Watts, Val J
• Ostrom, Rennolds S

Titel

Physiological roles of mammalian transmembrane adenylyl cyclase isoforms

Ist Teil von

• Physiological reviews, 2022-04, Vol.102 (2), p.815-857

Ort / Verlag

United States: American Physiological Society

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• Adenylyl cyclases (ACs) catalyze the conversion of ATP to the ubiquitous second messenger cAMP. Mammals possess nine isoforms of transmembrane ACs, dubbed AC1-9, that serve as major effector enzymes of G protein-coupled receptors (GPCRs). The transmembrane ACs display varying expression patterns across tissues, giving the potential for them to have a wide array of physiological roles. Cells express multiple AC isoforms, implying that ACs have redundant functions. Furthermore, all transmembrane ACs are activated by Gα , so it was long assumed that all ACs are activated by Gα -coupled GPCRs. AC isoforms partition to different microdomains of the plasma membrane and form prearranged signaling complexes with specific GPCRs that contribute to cAMP signaling compartments. This compartmentation allows for a diversity of cellular and physiological responses by enabling unique signaling events to be triggered by different pools of cAMP. Isoform-specific pharmacological activators or inhibitors are lacking for most ACs, making knockdown and overexpression the primary tools for examining the physiological roles of a given isoform. Much progress has been made in understanding the physiological effects mediated through individual transmembrane ACs. GPCR-AC-cAMP signaling pathways play significant roles in regulating functions of every cell and tissue, so understanding each AC isoform's role holds potential for uncovering new approaches for treating a vast array of pathophysiological conditions.