Question

Explain why a drug that interferes with the disassembly of a SNARE complex would block neurotransmission.

Short answer

The drug disrupts the recycling mechanism of the SNARE complex, due to which Q and R-SNAREs remain linked. As a result, the neurons are unable to release neurotransmitters.

Step-by-step solution

Introduction

SNAREs are lipid-linked proteins that mediate vesicle fusion with the membrane. In yeast, there are24 members, while in mammalian cells, there are more than 60. R-SNAREs (rich in conserved Arg residues) are found in vesicle membranes, while Q-SNAREs (rich in conserved Gln residues) are found in target membranes. The interactions between these proteins form a firm bond between the vesicle and the target membrane, a process known as docking. Thus, SNARES mediate the docking of synaptic vesicles.

Neurotransmission is blocked in the presence of drug

The components of a neuron's exocytotic machinery must be renewed for it to release neurotransmitters repeatedly. The four-helix SNARE complex is dismantled after synaptic vesicles fuse with the plasma membrane, leaving the Q-SNAREs in the plasma membrane. In contrast, sections of the membrane carrying R-SNAREs can be utilized to re-form synaptic vesicles. However, in the presence of the drug, the R- and Q-SNAREs remain linked; the neuron would eventually be unable to release neurotransmitters, and this recycling process would be impossible.