An evolutionarily conserved mechanism for presynaptic trapping

Abstract

Presynaptic differentiation takes place over three interrelated acts involving the biogenesis and trafficking of molecular complexes of active zone material, the "trapping" or stabilization of active zone sites, and the subsequent development of mature synapses. Although the identities of proteins involved with establishing presynaptic specializations have been increasingly delineated, the exact functional mechanisms by which the active zone is assembled remain poorly understood. Here, we discuss a theoretical model for how the trapping stage of presynaptic differentiation might occur in developing neurons. We suggest that subsets of active zone proteins containing polyglutamine domains undergo concentration-dependent prion-like conversions as they accumulate at the plasma membrane. This conversion might serve to aggregate the proteins into a singular structure, which is then able to recruit scaffolding agents necessary for regulated synaptic transmission. A brief informatics analysis in support of this 'Q' assembly hypothesis--across commonly used models of synaptogenesis--is presented.

Fig. 1

The amino acid sequence for each AZ protein was evenly divided into ten segments. The percentage of all of the protein’s Q residues that could be found in each individual segment is plotted as a temperature map. By and large, local Q domains (specified on the top of each map) were found in “hot” spots of the proteins where overall amino acid composition was biased towards Q residues. For perspective, known interaction motifs for each AZ protein are also delineated in white. The amino acid length of each protein is shown on the bottom right. All regional sizes are approximate. h human, m mouse, dm drosophila, ce C. elegans