17.9:
SNAREs and Membrane Fusion
For a vesicle to fuse with the target organelle, the lipid layers of the two membranes must be within one point five nanometers of each other.
In this proximity, lipids flow from one bilayer to the other by displacing water molecules around the membrane. This energetically unfavorable process requires specialized fusion proteins called SNAREs.
SNAREs are transmembrane proteins with helical motifs that catalyze membrane fusion.
SNAREs exist in complementary sets in the vesicle and target membranes as v-SNARE and t-SNARE.
The helical domains of t and v-SNAREs wrap around one another to form a trans-SNARE complex that initiates membrane fusion. The energy released upon trans-SNARE complex formation locks the two membranes together.
As the cytosolic sides of the bilayers move close together, they expel the water molecules at the interface. Now, lipid molecules freely flow from one leaflet to another, forming a connecting stalk.
During hemifusion, lipids in the outer leaflet mix to widen the zone of fusion. When the newly formed bilayer ruptures, fusion is complete.
SNAREs can remain in the membrane as stable complexes until they are needed for new rounds of membrane transport.
NSF, a hexameric ATPase, catalyzes SNARE disassembly. This ring-shaped protein feeds the SNARE complexes through its center to dissociate the t and v-SNAREs.
17.9:
SNAREs and Membrane Fusion
Once a transport vesicle has recognized its target organelle, the vesicular membrane needs to fuse with the target membrane to unload the cargo. Transmembrane proteins called SNAREs present on organelle membranes and their vesicles, mediate vesicle fusion.
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2 helical proteins, in the target membrane. The binding of the SNAREs results in forming an active and stable trans-SNARE complex that ensures that the vesicle has bound to the correct location to enable the accurate delivery of cargo.
Rab proteins regulate the inhibitory proteins associated with t-SNAREs to prevent incorrect vesicles from fusing to the target membrane. When the cognate vesicle is in the vicinity, Rab proteins recruit Rab effectors that release the inhibitory proteins and allow the formation of the trans-SNARE complex.
SNARE family of proteins are involved in many pathways such as the retrieval pathway at the ER and Golgi interface, autophagosome fusion with the lysosome, and several other processes such as fertilization of an ovum by sperm, myoblast fusion in muscle fibers, and targeted therapy for several viral diseases such as AIDs, where the viral membrane fuses to the plasma membrane. In animal cells, around 35 different SNAREs are known, each associated with specific organelles in the secretory and endocytic pathways.
Suggested Reading
- Han, J., Pluhackova, K., & Böckmann, R. A. (2017). The multifaceted role of SNARE proteins in membrane fusion. Frontiers in physiology, 8, 5.