SV2A Membrane Protein Introduction

Introduction of SV2A

SV2A is encoded by the SV2A gene which is located on 1q21.2. The molecular mass of SV2A is about 80 KDa. It belongs to the major facilitator superfamily of which members are membrane transport proteins, regulating the transport of small solutes in response to chemiosmotic gradients. SV2A is also a member of SV2 proteins which are abundant synaptic vesicle proteins, the other two are SV2B and SV2C, and they share the highly conserved transmembrane regions (TMRs) and the cytoplasmic loops connecting TMRs.

Function of SV2A Membrane Protein

SV2A is a synaptic vesicle protein. SV2A has protein kinase binding activity and transmembrane transporter activity. It is also related to the cellular calcium ion homeostasis and participates in chemical synaptic transmission, neurotransmitter transport and regulation of gamma-aminobutyric acid secretion and many other important biological processes. SV2A is generally present in almost all neurons, no matter what kind of their neurotransmitter type are. Besides, SV2A can regulate selectively low-frequency neurotransmission and take part in the control of regulated secretion in endocrine cells and neural. SV2A also maintains the readily releasable pool of secretory vesicles, by which it can regulate vesicle fusion positively. Accordingly, SV2A is a redundant Ca²⁺ regulator in neurotransmitter release. It is also identified as the brain binding site of a new antiepileptic drug, levetiracetam (LEV), which has a unique activity profile in animal models of seizure and epilepsy. Beyond that, SV2A plays an important role in the control of exocytosis.

Fig.1 (A) Models of the Inward and (B) Outward SV2A protein (Lee, 2015).

Application of SV2A Membrane Protein in Literature

1. Warnier C., et al. Enabling efficient PET imaging of Synaptic Vesicle glycoprotein 2A (SV2A) with a robust and one-step radiosynthesis of a highly potent (18)F-labelled ligand ([(18)F] UCB-H). Journal of Medicinal Chemistry. 2016, 59(19). PubMed ID: 27598384
   
   

   This article reveals the straightforward synthesis of a PET tracer for the imaging of synaptic vesicle glycoprotein 2A (SV2A). This work enables efficient and cost-effective clinical research on lots of neurological pathologies by the imaging of SV2A.

2. Rogawski M.A. A New SV2A Ligand for Epilepsy. Cell. 2016, 167(3):587-587. PubMed ID: 27768878
   
   

   Levetiracetam is able to bind to SV2A in synaptic and endocrine vesicles. An analog of levetiracetam, brivaracetam, is found to have higher affinity at racetam-binding sites and greater antiseizure potency.

3. Lee J., et al. Exploring the Interaction of SV2A with Racetams Using Homology Modelling, Molecular Dynamics and Site-Directed Mutagenesis. Plos One. 2015, 10(2): e0116589. PubMed ID: 25692762
   
   

   Authors in this group try to build models of both the inward and outward facing conformational states of SV2A and they use a sequence conservation analysis to guide the work. It will help people to further understand the ligand-binding site.

4. Stockburger C., et al. A Mitochondrial Role of SV2a Protein in Aging and Alzheimer's Disease: Studies with Levetiracetam. Journal of Alzheimers Disease Jad. 2015, 50(1):201. PubMed ID: 26639968
   
   

   This article suggests that interfering with the SV2a protein at the mitochondrial level and thereby improving mitochondrial function might represent an additional therapeutic effect of levetiracetam to improve symptoms of late-onset Alzheimer's disease.

5. Tokudome K., et al. Synaptic vesicle glycoprotein 2A (SV2A) regulates kindling epileptogenesis via GABAergic neurotransmission. Scientific Reports. 2016, 6(27420):27420. PubMed ID: 27265781
   
   

   This article suggests the role of SV2A in modulating epileptogenesis. Dysfunction of SV2A due to a mutation impairs the synaptic GABA release by reducing the Syt1 level and facilitates the kindling development. It reveals that SV2A-GABA system plays a crucial role in modulating kindling epileptogenesis.

SV2A Preparation Options

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Reference

1. Lee J., et al. (2015). Exploring the interaction of sv2a with racetams using homology modelling, molecular dynamics and site-directed mutagenesis. Plos One, 10(2), e0116589.

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