Abstract
Analysis of presynaptic protein expression in glutamatergic and GABAergic central synapses performed in several laboratories and with different techniques is unveiling a complex scenario, largely because each presynaptic protein exists in several isoforms. The interpretation of these findings is generally based on the notion that each synapse and each synaptic vesicle contains one of the isoforms of each family of presynaptic proteins. We verified whether this interpretation is tenable by performing triple labeling and immunoisolation studies with the aim of detecting two isoforms of a given presynaptic protein in glutamatergic or GABAergic axon terminals and/or synaptic vesicles (SVs). Here, we show that: (1) the possibility that not all families of presynaptic proteins are expressed in all terminals must be taken into serious account; (2) the expression of a given protein isoform in a terminal does not exclude the expression of other isoforms of the same protein in the same terminal and in the same vesicle. These conclusions open new and interesting problems; their experimental analysis might improve our understanding of the physiology and pathophysiology of central synapses.
Highlights
Neurotransmitter release is a fundamental process in synaptic communication, and heterogeneous expression of presynaptic proteins appears to contribute to functional differences, e.g., release probability, strength, and plasticity (Staple et al, 2000)
We reported the heterogeneous expression of couples of isoforms in vesicular glutamate transporter (VGLUT) 1−, VGLUT2− and vesicular GABA transporter (VGAT)-positive (+) axon terminals in rat cerebral cortex, and showed that VGLUT1+, VGLUT2+, and VGAT+ cortical axon terminals exhibit distinct expression profiles of presynaptic proteins (Bragina et al, 2007, 2010, 2012)
Based on the classical notion that each synapse contains at least one isoform of each family of presynaptic proteins (Jahn and Südhof, 1994), the most likely interpretation for this observation is that each VGLUT1 terminal expresses either STX1A or STX1B
Summary
Luca Bragina 1,2, Giorgia Fattorini 1,2, Silvia Giovedì 3, Federica Bosco 3, Fabio Benfenati 3,4 and Fiorenzo Conti 1,2,5*. Analysis of presynaptic protein expression in glutamatergic and GABAergic central synapses performed in several laboratories and with different techniques is unveiling a complex scenario, largely because each presynaptic protein exists in several isoforms. The interpretation of these findings is generally based on the notion that each synapse and each synaptic vesicle contains one of the isoforms of each family of presynaptic proteins. These conclusions open new and interesting problems; their experimental analysis might improve our understanding of the physiology and pathophysiology of central synapses
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