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This study challenges the widely accepted view that coronin proteins function primarily as actin-binding regulators. Researchers found that endogenous mammalian coronin proteins 1, 2, and 3 do not require F-actin for their cellular localization and that adding common research tags like GFP or FLAG to these proteins artificially increases their association with actin while disrupting their normal function. Instead, the evidence suggests coronin 2 and 3 regulate cAMP signaling independently of actin, indicating their primary role may be in cellular signaling rather than cytoskeletal regulation.
Why it matters
This research has significant implications for interpreting decades of coronin studies that relied on tagged proteins, potentially requiring reassessment of their conclusions. Understanding the true function of coronin proteins could lead to better insights into immune cell regulation and developmental processes, as these proteins control cell population sizes in mammals and are involved in critical biological processes.
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by Roko Gvozdenica Šipić, Haiyan Zhang, Andrii Kharin, Jerneja Koren, Viviana D’Otolo, Yuko Nariai, Takeshi Urano, Pawel Pelczar, Klemens Fröhlich, Alexander Schmidt, Urszula Brykczynska Kunzmann, Tohnyui Ndinyanka Fabrice, Alexey Baldin, Jean Pieters
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.
Source: Reassessment of the roles of coronin proteins as actin effectors and in signaling