Novel short isoforms of adenylyl cyclase as negative regulators of cAMP production.
Fiche publication
Date publication
juin 2018
Journal
Biochimica et biophysica acta
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DUCA Laurent
Tous les auteurs :
Vallin B, Legueux-Cajgfinger Y, Clément N, Glorian M, Duca L, Vincent P, Limon I, Blaise R
Lien Pubmed
Résumé
Here, we cloned a new family of four adenylyl cyclase (AC) splice variants from interleukin-1β (IL-1β)-transdifferentiated vascular smooth muscle cells (VSMCs) encoding short forms of AC8 that we have named "AC8E-H". Using biosensor imaging and biochemical approaches, we showed that AC8E-H isoforms have no cyclase activity and act as dominant-negative regulators by forming heterodimers with other full-length ACs, impeding the traffic of functional units towards the plasma membrane. The existence of these dominant-negative isoforms may account for an additional unsuspected degree of cAMP signaling regulation. It also reconciles the induction of an AC in transdifferentiated VSMCs with the vasoprotective influence of cAMP. The generation of alternative splice variants of ACs may constitute a generalized strategy of adaptation to the cell's environment whose scope had so far been ignored in physiological and/or pathological contexts.
Mots clés
Dominant-negative, Heterodimerization, Short adenylyl cyclases, Vascular smooth muscle cells, cAMP signaling
Référence
Biochim. Biophys. Acta. 2018 Jun 22;: