Reassessment of the roles of coronin proteins as actin effectors and in signaling.

Coronin proteins are present in all known non-plant eukaryotes, and are involved in key biological processes including cytoskeletal dynamics and the regulation of cell population sizes in amoeba and mammals. How, exactly, coronin proteins exert their function is debated. On the one hand, coronins are widely considered as F-actin-binding and regulatory proteins. On the other hand, coronin proteins were also shown to act as regulators of cAMP/Ca2+ signaling. Here, we demonstrate that endogenously expressed mammalian coronin 1, 2 and 3 did not depend on F-actin for their subcellular localization and did not impact actin-related processes that were previously reported to be coronin-dependent. We also show that the fusion of GFP or FLAG-tags to coronin proteins resulted in their increased colocalization with actin and phenocopied loss-of-function mutation in mice. Together these results suggest that inclusion of tags on coronin proteins causes increased colocalization with F-actin and can disrupt their in vivo function. Furthermore, we show that the ubiquitously expressed coronin 2 and coronin 3 regulated cAMP production regardless of the presence of F-actin. The analysis presented here may contribute to a re-evaluation of the function of coronin proteins in signaling, independently of actin modulation.