2.A.1.22.6
Synaptic vesicle 2C, SV2C or SLC22B3, of 727 aas and 11 TMSs. Botulinum neurotoxins (BoNTs) inhibit neurotransmitter release by selectively cleaving core components of the vesicular fusion machinery. The synaptic vesicle proteins Synaptotagmin-I and -II act as receptors for BoNT/B and BoNT/G. Mahrhold et al. 2006 showed that BoNT/A also interacts with a synaptic vesicle protein, the synaptic vesicle glycoprotein 2C (SV2C), but not with the homologous proteins SV2A and SV2B. Binding of BoNT/A occurs at the membrane juxtaposed region preceding transmembrane domain 8. A peptide comprising the intravesicular domain between transmembrane domains 7 and 8 specifically reduces the neurotoxicity of BoNT/A at phrenic nerve preparations, demonstrating the physiological relevance of this interaction (Mahrhold et al. 2006). The interactions of SV2C with BoNT have been reviewed (Li et al. 2020). SV2C is implicated in diseases such as Alzheimer's disease and Parkinson's disease (Stout et al. 2019). It seems to play roles in vesicle trafficking, exocytosis and neurotransmission (Hu et al. 2017).