Mazzotta, G.M., Bellanda, M., Minervini, G., Damulewicz, M., Cusumano, P., Aufiero, S., Stefani, M., Zambelli, B., Mammi, S., Costa, R., Tosatto, S.C.E. (2018). Calmodulin Enhances Cryptochrome Binding to INAD in Drosophila Photoreceptors.  Front. Mol. Neurosci. 11(): 280.

FBrf0239985

Research paper

Light is the main environmental stimulus that synchronizes the endogenous timekeeping systems in most terrestrial organisms. Drosophila cryptochrome (dCRY) is a light-responsive flavoprotein that detects changes in light intensity and wavelength around dawn and dusk. We have previously shown that dCRY acts through Inactivation No Afterpotential D (INAD) in a light-dependent manner on the Signalplex, a multiprotein complex that includes visual-signaling molecules, suggesting a role for dCRY in fly vision. Here, we predict and demonstrate a novel Ca2+-dependent interaction between dCRY and calmodulin (CaM). Through yeast two hybrid, coimmunoprecipitation (Co-IP), nuclear magnetic resonance (NMR) and calorimetric analyses we were able to identify and characterize a CaM binding motif in the dCRY C-terminus. Similarly, we also detailed the CaM binding site of the scaffold protein INAD and demonstrated that CaM bridges dCRY and INAD to form a ternary complex in vivo. Our results suggest a process whereby a rapid dCRY light response stimulates an interaction with INAD, which can be further consolidated by a novel mechanism regulated by CaM.

PMC6109769 (PMC) (EuropePMC)