Abstract
In a presynaptic nerve terminal, synaptic strength is determined by the pool of readily releasable vesicles (RRP) and the probability of release (P) of each RRP vesicle. These parameters are controlled at the active zone and vary across synapses, but how such synapse specific control is achieved is not understood. ELKS proteins are enriched at vertebrate active zones and enhance P at inhibitory hippocampal synapses, but ELKS functions at excitatory synapses are not known. Studying conditional knockout mice for ELKS, we find that ELKS enhances the RRP at excitatory synapses without affecting P. Surprisingly, ELKS C-terminal sequences, which interact with RIM, are dispensable for RRP enhancement. Instead, the N-terminal ELKS coiled-coil domains that bind to Liprin-α and Bassoon are necessary to control RRP. Thus, ELKS removal has differential, synapse-specific effects on RRP and P, and our findings establish important roles for ELKS N-terminal domains in synaptic vesicle priming.
Highlights
Within a presynaptic nerve terminal, synaptic vesicle exocytosis is restricted to sites of neurotransmitter release called active zones
ELKS1a and ELKS2a are enriched at excitatory hippocampal synapses
We employed immunostainings for ELKS1a and ELKS2a in cultured hippocampal neurons and analyzed their distribution using confocal microscopy. Both ELKS proteins were present at excitatory and inhibitory synapses and we observed higher intensity staining at excitatory synapses compared to inhibitory synapses for ELKS1a and ELKS2a (Figure 1B)
Summary
Within a presynaptic nerve terminal, synaptic vesicle exocytosis is restricted to sites of neurotransmitter release called active zones. A small subset of the synaptic vesicles are primed in close proximity to presynaptic Ca2+ channels such that the incoming action potential leads to neurotransmitter release with minimal delay. The proteins of the active zone control the size of this pool of primed, readily releasable vesicles (RRP) and the release probability of those vesicles in response to an action potential (Kaeser and Regehr, 2014; Alabi and Tsien, 2012). It is well known that RRP size and vesicular release probability differ across synapses, contributing to the generation of unique release properties (Abbott and Regehr, 2004). The underlying molecular mechanisms that control RRP and P are still only partially understood, and it is not known what components of the release machinery account for their synapse specific control
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