Novel short isoforms of adenylyl cyclase as negative regulators of cAMP production

Publication date: September 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1865, Issue 9Author(s): Benjamin Vallin, Yohan Legueux-Cajgfinger, Nathalie Clément, Martine Glorian, Laurent Duca, Pierre Vincent, Isabelle Limon, Régis BlaiseAbstractHere, 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 unsuspected additional 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.
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - Category: Molecular Biology Source Type: research