Identification of a novel interaction between α‐synuclein and VMAT2

• DOI: 10.1096/fasebj.22.1_supplement.715.6
• Publication Date: 2021-06-21T23:28:05Z
• Authors: E. Danielle Dean; Kennie Raviie She...; Yingjie Li; Gonzalo E. Torres; Gary W. Miller
• Keywords: Colocalization; Vesicular monoamine transporter

Several familial forms of Parkinson disease are linked to mutations in α‐synuclein (α‐syn), a major component Lewy bodies. One proposed role for α‐syn dopaminergic neurons is the maintenance dopamine (DA) homeostasis. We have identified an interaction with and vesicular monoamine transporter 2 (VMAT2). VMAT2 sequesters cytosolic DA into vesicles release at synaptic terminals. Here, we show between C‐terminus by yeast two‐hybrid assay. This confirmed coimmunoprecipitation SHSY5Y cells. Immunofluorescence confocal microscopy shows both perinuclear punctate neuritic‐like colocalization heterologously coexpressing cells natively‐expressing primary mouse nigral neurons. staining consistent vesicle compartment such as golgi or endoplasmic reticulum. Finally, coexpression increases tetrabenazine sensitive‐VMAT2 sequestration 3 H‐DA cell lysates. increase activity reflective 2‐fold V max . These data suggest that one function may be maintain proper storage via regulation VMAT2. Since also protects from oxidation, high protect death. Supported U54ES‐012068.