A toolbox of fluorescence microscopic approaches reveals dynamics and assembly of a membrane-associated protein.

Aggregation and oligomerization have often been challenging yet exciting aspects in the study of membraneassociated proteins (1). The motivation for exploring oligomerization of membrane proteins derives from the emerging realization that oligomerization holds the key to efficient drug discovery (2). Although oligomerization is an important step for membrane proteins, dynamics play a crucial role in protein function in membranes. Unfortunately, oligomerization studies often do not address the issue of dynamics (and vice versa). In this issue of the Biophysical Journal, Crosby et al. (3) describe a comprehensive study in which both assembly and dynamics of a membrane-associated protein, annexin A4, are explored. The elegance of this article lies in arriving at a model of annexin assembly at the plasma membrane, by an intelligent combination of complimentary fluorescence microscopic approaches that could provide useful insight into its function. A summary of the key membraneassociated processes along with the measurement techniques utilized in the study of Crosby et al. (3) is shown in Fig. 1. Crosby et al. (3) examined