Synaptic vesicle binding of α-synuclein is modulated by β- and γ-synucleins

a-synuclein, b-synuclein, and g-synuclein are abundantly expressed proteins in the vertebrate nervous system. a-synuclein functions in neurotransmitter release by binding to and clustering synaptic vesicles and chaperoning SNARE-complex assembly. Pathologically, aggregates originating from soluble pools of a-synuclein are deposited into Lewy bodies in Parkinson’s disease and related synucleinopathie

Synaptic vesicle binding of α-synuclein is modulated by β- and γ-synucleins

α-synuclein, β-synuclein, and γ-synuclein are abundantly expressed proteins in the vertebrate nervous system. α-synuclein functions in neurotransmitter release by binding to and clustering synaptic vesicles and chaperoning SNARE-complex assembly. Pathologically, aggregates originating from soluble pools of α-synuclein are deposited into Lewy bodies in Parkinson’s disease and related synucleinopathies. The functions of β-synuclein and γ-synuclein in presynaptic terminals remain poorly studied. Using in vitro liposome binding studies, circular dichroism spectroscopy, immunoprecipitation, and fluorescence resonance energy transfer (FRET) experiments on isolated synaptic vesicles in combination with subcellular fractionation of brains from synuclein mouse models, we show that β-synuclein and γ-synuclein have a reduced affinity toward synaptic vesicles compared with α-synuclein, and that heteromerization of β-synuclein or γ-synuclein with α-synuclein results in reduced synaptic vesicle binding of α-synuclein in a concentration-dependent manner. Our data suggest that β-synuclein and γ-synuclein are modulators of synaptic vesicle binding of α-synuclein and thereby reduce α-synuclein’s physiological activity at the neuronal synapse

Malaya, 1948: Britain’s Asian Cold War?

Between 8:30 and 9:00 a.m. on 16 June 1948, three Europeans were shot dead in the Sungei Siput area of Perak in northern Malaya. The three were estate managers of rubber plantations, and the perpetrators were guerrillas in the “mobile corps” of the Malayan Communist Party (MCP). The shootings were the culmination of a long series of attacks and “outrages” against estate managers in Penang, Selangor, and the southern state of Johore. Late that afternoon, the colonial government declared a state of emergency in Perak and Johore that was extended, two days later, to the whole ofMalaya. An immediate casualty was respect for civil liberties. Under emergency regulations the authorities enacted a range of draconian measures, including a ban on “seditious” publications; the introduction of coercive powers of detention, arrest, trial, deportation, and “banishment”; the establishment of the death penalty for anyone carrying unauthorized ªrearms; and the registration of the entire adult population