Abstract
The mechanism of postsynaptic neurotransmitter receptor clustering has been best described at the neuromuscular junction (NMJ), where packets of nicotinic acetylcholine receptors (nAChRs) in muscle fibre are redistributed to the synaptic site upon motor neuron innervation. This process of receptor localisation is facilitated by agrin signalling, and the stability of the resulting nAChR clusters depends upon the activation of Src family kinases (SFKs). In contrast to the NMJ however, the cellular signalling mechanisms orchestrating the clustering of nAChRs in the central nervous system (CNS) remain poorly defined. Furthermore, our understanding of the role of SFKs in the CNS is also limited. Here we provide evidence that SFK activation is required for synapse formation between pairs of identified neurons isolated from the CNS of Lymnaea stagnalis. Furthermore, we suggest that SFKs are involved in the functional redistribution of nAChRs to the synaptic contact sites in isolated axons. To the best of our knowledge, this study is the first to demonstrate a role for SFKs in the clustering of nAChRs in central neurons, suggesting that the mechanisms of receptor clustering between the peripheral and central nervous system are likely conserved.
Highlights
The model synapse used to study synaptogenesis is the neuromuscular junction (NMJ), as it is large and experimentally accessible in most preparations (Madhavan and Peng, 2005; Darabid et al, 2014)
We have previously shown that excitatory synapse formation between soma–soma pairs of individually identified L. stagnalis neurons requires an extrinsic source of neurotrophic factors
Excitatory synapse formation between the presynaptic neuron VD4 and the postsynaptic neuron LPeD1 relies upon activity-induced calcium influx in LPeD1, activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) cascade, and expression of the transcription factor, Lymnaea menin, which are required for the expression of excitatory nicotinic acetylcholine receptors (nAChRs) (Xu et al, 2009; Flynn et al, 2014)
Summary
The model synapse used to study synaptogenesis is the neuromuscular junction (NMJ), as it is large and experimentally accessible in most preparations (Madhavan and Peng, 2005; Darabid et al, 2014). The cardinal feature of NMJ development is the redistribution of postsynaptic nicotinic acetylcholine receptors (nAChRs) to the site of nerve-muscle contact, following innervation of the muscle by motor neurons (Mejat et al, 2003; Darabid et al, 2014). The process of nAChR clustering is initiated by agrin, a proteoglycan predominantly released by neurons and localized in the basal lamina (Yang and Nelson, 2004; Ghazanfari et al, 2011; Darabid et al, 2014).
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