Abstract
BackgroundCollybistin (CB), a neuron-specific guanine nucleotide exchange factor, has been implicated in targeting gephyrin-GABAA receptors clusters to inhibitory postsynaptic sites. However, little is known about additional CB partners and functions.FindingsHere, we identified the p40 subunit of the eukaryotic translation initiation factor 3 (eIF3H) as a novel binding partner of CB, documenting the interaction in yeast, non-neuronal cell lines, and the brain. In addition, we demonstrated that gephyrin also interacts with eIF3H in non-neuronal cells and forms a complex with eIF3 in the brain.ConclusionsTogether, our results suggest, for the first time, that CB and gephyrin associate with the translation initiation machinery, and lend further support to the previous evidence that gephyrin may act as a regulator of synaptic protein synthesis.
Highlights
Collybistin (CB), a neuron-specific guanine nucleotide exchange factor, has been implicated in targeting gephyrin-GABAA receptors clusters to inhibitory postsynaptic sites
Together, our results suggest, for the first time, that CB and gephyrin associate with the translation initiation machinery, and lend further support to the previous evidence that gephyrin may act as a regulator of synaptic protein synthesis
Our results demonstrate that CB is associated with the translation initiation complex, and suggest that CB, along with gephyrin, may be involved in the regulation of protein synthesis at postsynaptic sites
Summary
Our results suggest, for the first time, that CB and gephyrin associate with the translation initiation machinery, and lend further support to the previous evidence that gephyrin may act as a regulator of synaptic protein synthesis. Despite our expanding knowledge in this area, the functions of several synaptic proteins, mainly those regulating the development and plasticity of inhibitory synapses, remain to be explored further. It has recently been shown that the SH3 domain of CB interacts with neuroligin 2, a postsynaptic cell adhesion protein [9], and with the GABAA receptor a2 subunit [10], and these interactions seem to relieve the inhibitory effect of this domain, rendering the CBSH3+ variants, the predominant brain and spinal cord isoforms, active in targeting gephyrin scaffolds to the plasma membrane. Our results demonstrate that CB is associated with the translation initiation complex, and suggest that CB, along with gephyrin, may be involved in the regulation of protein synthesis at postsynaptic sites
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