Genetically encoded lipid biosensors

Abstract

Lipids convey both structural and functional properties to eukaryotic membranes. Understanding the basic lipid composition and the dynamics of these important molecules, in the context of cellular membranes, can shed light on signaling, metabolism, trafficking, and even membrane identity. The development of genetically encoded lipid biosensors has allowed for the visualization of specific lipids inside individual, living cells. However, a number of caveats and considerations have emerged with the overexpression of these biosensors. In this Technical Perspective, we provide a current list of available genetically encoded lipid biosensors, together with criteria that determine their veracity. We also provide some suggestions for the optimal utilization of these biosensors when both designing experiments and interpreting results.

FIGURE 1:

Ceci n'est pas une PIP (“This is not a PIP”). This COS-7 cell is expressing GFP-P4C, a PI4P biosensor. The images show the cell before and after a treatment that induces relocalization of the probe. What do you suppose this treatment was? Read the text for the answer.

FIGURE 2:

Go high or go low (affinity). These HeLa cells are expressing either a monomeric (top) or a dimeric (bottom) version of GFP-P4M, a PI4P biosensor. The images show the cells before and after activation of a 5-phosphatase that increases PI4P in the plasma membrane. The lower affinity biosensor is able to detect small changes in PI4P synthesis and relocalize to the PM (note how the cytoplasm looks dimmer in the “after” image), whereas the higher-affinity probe is already saturated at the plasma membrane.