Fig. 6

The proposed action model and pathway of βγ-CAT. As a vertebrate-secreted ALP and TFF protein complex, βγ-CAT exerts its functions via an assembly process. The actions of assembled βγ-CAT can be divided into four steps. Step 1. Membrane binding. Once the assembled βγ-CAT encounters target cells, βγ-CAT is subsequently anchored to lipid raft microdomains on the plasma membrane. Therefore, the BmALP1 subunit of βγ-CAT binds to the extracellular glycan headgroup of gangliosides, and the BmTFF3 subunit of βγ-CAT binds to the extracellular glycan headgroup of sulfatides. Step 2. After βγ-CAT binding to the membrane, the BmTFF3 subunit detaches from the membrane, and the BmALP1 subunit of βγ-CAT is endocytosed and enters the cell. Step 3. The endocytic βγ-CAT then oligomerizes and forms pores in the membranes of endolysosomes. Step 4. The formed pores induce a flux of substances, such as ions, ultimately regulating the properties of endolysosomes. As we observed previously, changes in the properties of endolysosomes can trigger various effects, such as the expulsion of pathogen-containing vesicles¹⁶ and increased lysosome destabilization, leading to inflammasome-dependent IL-1β release¹⁵ and tissue repair¹⁰