Visualizing CaMKII and CaM activity: a paradigm of compartmentalized signaling

Calcium (Ca2+) has long been recognized as a crucial intracellular messenger attaining stimuli-specific cellular outcomes via localized signaling. Ca2+-binding proteins, such as calmodulin (CaM), and its target proteins are key to the segregation and refinement of these Ca2+-dependent signaling events. This review not only summarizes the recent technological advances enabling the study of subcellular Ca2+-CaM and Ca2+-CaM-dependent protein kinase (CaMKII) signaling events but also highlights the outstanding challenges in the field.