Biomedical
Room for Two: The Synaptophysin/Synaptobrevin Complex
Peer Reviewed
Abstract
Synaptic vesicle release is regulated by upwards of 30 proteins at the fusion complex alone, but disruptions in any one of these components can have devastating consequences for neuronal communication. Aberrant molecular responses to calcium signaling at the pre-synaptic terminal dramatically affect vesicle trafficking, docking, fusion, and release. At the organismal level, this is reflected in disorders such as epilepsy, depression, and neurodegeneration. Among the myriad pre-synaptic proteins, perhaps the most functionally mysterious is synaptophysin (SYP). On its own, this vesicular transmembrane protein has been proposed to function as a calcium sensor, a cholesterol-binding protein, and to form ion channels across the phospholipid bilayer. The downstream effects of these functions are largely unknown. The physiological relevance of SYP is readily apparent in its interaction with synaptobrevin (VAMP2), an integral element of the neuronal SNARE complex. SNAREs, soluble NSF attachment protein receptors, comprise a family of proteins essential for vesicle fusion. The complex formed by SYP and VAMP2 is thought to be involved in both trafficking to the pre-synaptic membrane as well as regulation of SNARE complex formation. Recent structural observations specifically implicate the SYP/VAMP2 complex in anchoring the SNARE assembly at the pre-synaptic membrane prior to vesicle fusion. Thus, the SYP/VAMP2 complex appears vital to the form and function of neuronal exocytotic machinery.
Key Questions about 'Room for Two: The Synaptophysin/Synaptobrevin Complex'
The article *"Room for Two: The Synaptophysin/Synaptobrevin Complex"* by Dustin N. White and Michael H. B. Stowell, published in *Frontiers in Synaptic Neuroscience* in September 2021, investigates the interaction between synaptophysin (SYP) and synaptobrevin (VAMP2) in the regulation of synaptic vesicle release. Source
1. What is the role of synaptophysin (SYP) in synaptic vesicle release?
Synaptophysin (SYP) is a vesicular transmembrane protein whose functions have been proposed to include acting as a calcium sensor, a cholesterol-binding protein, and forming ion channels across the phospholipid bilayer. However, the downstream effects of these functions are largely unknown. Source
2. How does the SYP/VAMP2 complex contribute to synaptic vesicle release?
The complex formed by SYP and VAMP2 is thought to be involved in both trafficking to the pre-synaptic membrane and regulation of SNARE complex formation. Recent structural observations specifically implicate the SYP/VAMP2 complex in anchoring the SNARE assembly at the pre-synaptic membrane prior to vesicle fusion. Source
3. What are the implications of the SYP/VAMP2 complex in neurological disorders?
Disruptions in the components of the SYP/VAMP2 complex can have devastating consequences for neuronal communication, affecting vesicle trafficking, docking, fusion, and release. At the organismal level, this is reflected in disorders such as epilepsy, depression, and neurodegeneration. Source
