Fig. 2: Application of PL in neuroscience.

This schematic illustrates how PL enzymes are used to study spatially resolved proteomic interactions in the nervous system. The top panel depicts two major strategies for PL enzyme delivery: a Cre-independent method using AAVs driven by cell-type-specific promoters, and a Cre-dependent method using floxed PL constructs in Cre-transgenic animals. These approaches allow selective expression of enzymes such as APEX, BioID2, TurboID or HRP in specific neuronal or glial populations. Once expressed, PL enzymes can be targeted to distinct subcellular compartments—for example, cytosolic TurboID enables broad labeling within the cytoplasm of defined cells. The bottom panel illustrates the use of PL for probing intercellular proteomic environments, including synaptic interfaces. Split-TurboID, in particular, enables selective labeling at cell–cell contact sites by reconstituting enzyme activity when complementary fragments are expressed in interacting cell types, such as neurons and astrocytes, allowing precise mapping at the tripartite synapse.