Cytosolic Targeting Domains of ! and " Calmodulin-dependent Protein Kinase II*

Ca2#/calmodulin-dependent protein kinase II (CaMKII) isozyme variability is the result of alternative usage of variable domain sequences. Isozyme expression is cell type-specific to transduce the appropriate Ca2# signals. We have determined the subcellular targeting domain of "E CaMK-II, an isozyme that induces neurite outgrowth, and of a structurally similar isozyme, !C CaMK-II, which does not induce neurite outgrowth. "E CaMK-II co-localizes with filamentous actin in the perinuclear region and in cellular extensions. In contrast, !C CaMK-II is uniformly cytosolic. Constitutively active "E CaMK-II induces F-actin-rich extensions, thereby supporting a functional role for its localization. C-terminal constructs, which lack central variable domain sequences, can oligomerize and localize like full-length "E and !C CaMK-II. Central variable domains themselves are monomeric and have no targeting capability. The C-terminal 95 residues of " CaMK-II also has no targeting capability but can efficiently oligomerize. These findings define a targeting domain for ! and " CaMK-IIs that is in between the central variable and association domains. This domain is responsible for the subcellular targeting differences between ! and " CaMK-IIs.