Coronin 3 is a ubiquitously expressed member of the coronin protein family in mammals. In fibroblasts and HEK 293 cells, it is localized both in the cytosol and in the submembranous cytoskeleton, especially at lamellipodia and membrane ruffles. The carboxyl terminus of all coronins contains a coiled coil suggested to mediate dimerization. We show here that in contrast to other coronin homologues, the recombinant human coronin 3 carboxyl terminus forms oligomers rather than dimers, and that this part is sufficient to bind to and cross-link F-actin in vitro. The carboxyl terminus alone also conferred membrane association in vivo, and removal of the coiled coil abolished membrane localization but not in vitro F-actin binding. Coronin 3 is exclusively extracted as an oligomer from both the cytosol and the membrane fraction. Because oligomerization was not reported for other coronins, it might be a key feature governing coronin 3-specific functions. Cytosolic coronin 3 showed a high degree of phosphorylation, which is likely to regulate the subcellular localization of the protein.

Coronins belong to the fundamental WD40-repeat proteins. They are mainly found at the submembraneous area, they bind F-actin in vitro, and most of the seven mammalian coronins have unclear roles. Coronin 3 is abundantly expressed in the adult CNS. All murine brain areas express coronin 3 during embryogenesis and the first postnatal stages. Expression in grey matter decreases postnatally, except for hippocampal pyramidal and dentate gyrus neurons, and cerebellar Purkinje cells, while levels in white matter increase in the course of myelination. Consistently, coronin 3 is abundant in differentiating neuro-2a and PC-12 cells and in primary oligodendrocytes. Treatment with PKC activator PMA reduced coronin 3 protein levels. To address its functions, neuro-2a and PC-12 cells were transfected with GFP-tagged coronin 3 versions. Full-length coronin 3 among other areas localized to outgrowing neurites, whereas truncated proteins efficiently suppressed neurite formation. Our results favour a role for coronin 3 in neuron morphogenesis and possibly migration.