The evolutionarily conserved protein coronin 1 is needed for activating the cyclic AMP signaling pathway in the brain and is important for cognition and behavior.

Multicellular development of Dictyostelium is induced by starvation and is crucial for its long-term survival. Coronin A mediates the transition from growth to development of the cells and initiates the cAMP-dependent relay by regulating the response to secreted cell density and nutrient deprivation factors.

Edited by Lukas HuberCoronins constitute a family of conserved proteins expressed in all eukaryotes that have been implicated in the regulation of a wide variety of cellular activities. Recent work showed an essential role for coronin 1 in the modulation of the cAMP/PKA pathway in neurons through the interaction of coronin 1 with the G protein subtype Gas in a stimulus-dependent manner, but the molecular mechanism regulating coronin 1-Gas interaction remains unclear. We here show that phosphorylation of coronin 1 on Thr 418/424 by cyclin-dependent kinase (CDK) 5 activity was responsible for coronin 1-Gas association and the modulation of cAMP production. Together these results show an essential role for CDK5 activity in promoting the coronin 1-dependent cAMP/PKA pathway.

Coronin proteins are widely expressed among eukaryotic organisms. Most coronins consist of a WD‐repeat domain followed by a C‐terminal coiled coil. Dictyostelium discoideum expresses a single short coronin coronin A, which has been implicated in both actin modulation and multicellular differentiation. Whether coronin A's coiled coil is important for functionality, as well as the oligomeric state of coronin A is not known. Here, we show that the coiled‐coil domain in Dictyostelium coronin A functions in homodimerization, is dispensable for coronin A stability and localization but essential for multicellular differentiation. These results allow a better understanding of the role for the coiled‐coil domain of coronin A in oligomerization and demonstrate that its presence is essential for multicellular differentiation.

Coronin proteins are evolutionary conserved WD repeat containing proteins that have been proposed to carry out different functions. In Dictyostelium, the short coronin isoform, coronin A, has been implicated in cytoskeletal reorganization, chemotaxis, phagocytosis and the initiation of multicellular development. Generally thought of as modulators of F-actin, coronin A and its mammalian homologs have also been shown to mediate cellular processes in an F-actin-independent manner. Therefore, it remains unclear whether or not coronin A carries out its functions through its capacity to interact with F-actin. Moreover, the interacting partners of coronin A are not known. Here, we analyzed the interactome of coronin A as well as its interaction with F-actin within cells and in vitro. Interactome analysis showed the association with a diverse set of interaction partners, including fimbrin, talin and myosin subunits, with only a transient interaction with the minor actin10 isoform, but not the major form of actin, actin8, which was consistent with the absence of a coronin A-actin interaction as analyzed by co-sedimentation from cells and lysates. In vitro, however, purified coronin A co-precipitated with rabbit muscle F-actin in a coiled-coil-dependent manner. Our results suggest that an in vitro interaction of coronin A and rabbit muscle actin may not reflect the cellular interaction state of coronin A with actin, and that coronin A interacts with diverse proteins in a time-dependent manner.