Minimal functional domains of the core polarity regulator Dlg

Khoury, Mark J.; Bilder, David

doi:10.1101/2022.04.29.490107

Cited by 1 publication

(1 citation statement)

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“…DLG1 functions in many diverse tissues including and beyond the nervous system and plays multiple roles in cell adhesion, synaptic organization, and cell polarity (Bilder et al, 2000, 2003; Khoury and Bilder, 2022; Su et al, 2013; Tepass et al, 2001; Woods and Bryant, 1991). The broad functional roles of DLG1 are mediated by several translational isoforms generated from alternative STOP codons (Fig.…”

Section: Discussionmentioning

confidence: 99%

A conditional strategy for cell-type specific labeling of endogenous excitatory synapses inDrosophilareveals subsynaptic architecture

Parisi

Aimino

Mosca

2022

Preprint

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Chemical neurotransmission occurs at specialized contacts where presynaptic neurotransmitter release machinery apposes clusters of postsynaptic neurotransmitter receptors and signaling molecules. A series of elegantly complex events underlies the recruitment of pre- and postsynaptic proteins to sites of neuronal connection and enables the correct three-dimensional synaptic organization that underlies circuit processing and computation. To better study the developmental events of synaptogenesis in individual neurons, we need cell-type specific strategies to visualize the individual proteins at their endogenous levels at synapses. Though such strategies exist for a variety of presynaptic proteins, postsynaptic proteins remain less studied due to a paucity of reagents that allow visualization of endogenous individual postsynapses in a cell-type specific manner. To study excitatory postsynapses, we engineered dlg1[4K], a conditional, epitope-tagged marker of the excitatory postsynaptic density in Drosophila. In combination with binary expression systems, dlg1[4K] effectively labels postsynaptic regions at both peripheral neuromuscular and central synapses in larvae and adults. Using dlg1[4K], we find that distinct rules govern the postsynaptic organization of different adult neuron classes, that multiple binary expression systems can concurrently label pre- and postsynaptic regions of synapses in a cell-type-specific manner, and for the first time, visualize neuronal DLG1 at the neuromuscular junction. These results validate a novel strategy for conditional postsynaptic labeling without the caveats of overexpression and demonstrate new principles of subsynaptic organization. The use of dlg1[4K] marks a notable advancement in studying cell-type specific synaptic organization in Drosophila and the first example of a general postsynaptic marker to complement existing presynaptic strategies.

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