Higher-order Organization and Regulation of Adenylyl Cyclases

There is increasing awareness of the compartmentalization of cAMP signalling--the means by which cAMP levels change in discrete domains of the cell with discrete local consequences. Current developments in understanding the organization of adenylyl cyclases in the plasma membrane are illuminating how the earliest part of cAMP compartmentalization could occur. This review focuses on recent findings regarding three levels of adenylyl cyclase organization--oligomerization, positioning to lipid rafts and participation in multiprotein signalling complexes. This organization, coupled with the role of scaffolding proteins in arranging the downstream effectors of cAMP, helps to identify complexes that greatly facilitate the translation of enzyme activation into local consequences.