ABSTRACT
The cytosolic proteins synucleins and synapsins are thought to play cooperative roles in regulating synaptic vesicle (SV) recycling, but mechanistic insight is lacking. Here, we identify the synapsin E-domain as an essential functional binding-partner of α-synuclein (α-syn). Synapsin E-domain allows α-syn functionality, binds to α-syn, and is necessary and sufficient for enabling effects of α-syn at synapses of cultured mouse hippocampal neurons. Together with previous studies implicating the E-domain in clustering SVs, our experiments advocate a cooperative role for these two proteins in maintaining physiologic SV clusters.
Subject(s)
Hippocampus , Neurons , Synapsins , alpha-Synuclein , Animals , Humans , Mice , alpha-Synuclein/metabolism , alpha-Synuclein/genetics , alpha-Synuclein/chemistry , Cells, Cultured , Hippocampus/metabolism , Neurons/metabolism , Protein Binding , Protein Domains , Synapses/metabolism , Synapsins/metabolism , Synapsins/genetics , Synaptic Vesicles/metabolismABSTRACT
The cytosolic proteins synucleins and synapsins are thought to play cooperative roles in regulating synaptic vesicle (SV) recycling, but mechanistic insight is lacking. Here we identify the synapsin E-domain as an essential functional binding-partner of α-synuclein (α-syn). Synapsin E-domain allows α-syn functionality, binds to α-syn, and is necessary and sufficient for enabling effects of α-syn at the synapse. Together with previous studies implicating the E-domain in clustering SVs, our experiments advocate a cooperative role for these two proteins in maintaining physiologic SV clusters.
ABSTRACT
The incidence of symptomatic vasculitis in human immunodeficiency virus (HIV)-infected patients is approximately 1%, and it commonly presents as arterial occlusive disease or aneurysmal disease. Early diagnosis of vascular complications in those patients is essential; however, it is extremely challenging. Iliac aneurysms are usually silent, and because of their deep location, detection of these aneurysms is typically difficult. Therefore, they always continue to be asymptomatic until rupture unless they are discovered incidentally on a radiological investigation for an irrelative condition. We present the case of a 61-year-old HIV-positive man with bilateral iliac aneurysms and total coronary artery occlusion presenting with a leg ulcer.
ABSTRACT
The normal function of α-synuclein (α-syn) remains elusive. Although recent studies suggest α-syn as a physiologic attenuator of synaptic vesicle (SV) recycling, mechanisms are unclear. Here, we show that synapsin-a cytosolic protein with known roles in SV mobilization and clustering-is required for presynaptic functions of α-syn. Our data offer a critical missing link and advocate a model where α-syn and synapsin cooperate to cluster SVs and attenuate recycling.
