Molecular Architecture of Genetically-Tractable GABA Synapses in C. elegans

Zhou, Xin J.; Bessereau, Jean-Louis

doi:10.3389/fnmol.2019.00304

Cited by 18 publications

(9 citation statements)

References 70 publications

(78 reference statements)

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“…It arose via gene duplication in stem vertebrates, which strongly suggests that the Collybistin/Gephyrin-based GABAergic and glycinergic postsynaptic scaffold exists only in vertebrates. Supporting this, Collybistin and Gephyrin appear to be absent from the GABAergic postsynapse in nematodes [84] (which may thus have evolved independently from the vertebrate GABAergic postsynapse).…”

Section: Modules Of the Inhibitory Postsynapsementioning

confidence: 77%

The Evolutionary Assembly of Neuronal Machinery

Arendt

2020

Current Biology

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Neurons are highly specialized cells equipped with a sophisticated molecular machinery for the reception, integration, conduction and distribution of information. The evolutionary origin of neurons remains unsolved. How did novel and pre-existing proteins assemble into the complex machinery of the synapse and of the apparatus conducting current along the neuron? In this review, the step-wise assembly of functional modules in neuron evolution serves as a paradigm for the emergence and modification of molecular machinery in the evolution of cell types in multicellular organisms. The pre-synaptic machinery emerged through modification of calcium-regulated large vesicle release, while the postsynaptic machinery has different origins: the glutamatergic postsynapse originated through the fusion of a sensory signaling module and a module for filopodial outgrowth, while the GABAergic postsynapse incorporated an ancient actin regulatory module. The synaptic junction, in turn, is built around two adhesion modules controlled by phosphorylation, which resemble septate and adherens junctions. Finally, neuronal action potentials emerged via a series of duplications and modifications of voltage-gated ion channels. Based on these origins, key molecular innovations are identified that led to the birth of the first neuron in animal evolution.

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Section: Modules Of the Inhibitory Postsynapsementioning

confidence: 77%

The Evolutionary Assembly of Neuronal Machinery

Arendt

2020

Current Biology

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“…Notably, the transcript for MADD-4/punctin, a secreted protein that has been shown to direct process outgrowth as well synaptic placement (Zhou and Bessereau, 2019), is significantly enriched in stratum 1 neurons. In addition, tsp-7, which is highly expressed in most neurons of stratum 2, is homologous to the human protein CD63, a member of the tetraspanin superfamily.…”

Section: Analysis Of Cis-regulatory Elements Reveals a Rich Array Of mentioning

confidence: 99%

Molecular topography of an entire nervous system

Taylor

Santpere

Weinreb

et al. 2020

Preprint

262

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SummaryNervous systems are constructed from a deep repertoire of neuron types but the underlying gene expression programs that specify individual neuron identities are poorly understood. To address this deficit, we have produced an expression profile of all 302 neurons of the C. elegans nervous system that matches the single cell resolution of its anatomy and wiring diagram. Our results suggest that individual neuron classes can be solely identified by combinatorial expression of specific gene families. For example, each neuron class expresses unique codes of ∼23 neuropeptide-encoding genes and ∼36 neuropeptide receptors thus pointing to an expansive “wireless” signaling network. To demonstrate the utility of this uniquely comprehensive gene expression catalog, we used computational approaches to (1) identify cis-regulatory elements for neuron-specific gene expression across the nervous system and (2) reveal adhesion proteins with potential roles in synaptic specificity and process placement. These data are available at cengen.org and can be interrogated at the web application CengenApp. We expect that this neuron-specific directory of gene expression will spur investigations of underlying mechanisms that define anatomy, connectivity and function throughout the C. elegans nervous system.

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“…It triggers the postsynaptic clustering of type A GABA receptors (GABA A Rs) at GABAergic NMJs. At cholinergic NMJs, it associates with Punctin L and inhibits the inappropriate recruitment of GABA A Rs by Punctin L. Punctin S controls the clustering of GABA A Rs by two convergent molecular pathways (for review, see Zhou and Bessereau 2019 ). First, Punctin S binds and clusters the synaptic adhesion molecule NLG-1/neuroligin in front of GABAergic boutons, which controls the synaptic localization of GABA A Rs ( Maro et al, 2015 ; Tu et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

The HSPG syndecan is a core organizer of cholinergic synapses

Zhou

Vachon

Cizeron

et al. 2021

Journal of Cell Biology

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The extracellular matrix has emerged as an active component of chemical synapses regulating synaptic formation, maintenance, and homeostasis. The heparan sulfate proteoglycan (HSPG) syndecans are known to regulate cellular and axonal migration in the brain. They are also enriched at synapses, but their synaptic functions remain more elusive. Here, we show that SDN-1, the sole orthologue of syndecan in C. elegans, is absolutely required for the synaptic clustering of homomeric α7-like acetylcholine receptors (AChRs) and regulates the synaptic content of heteromeric AChRs. SDN-1 is concentrated at neuromuscular junctions (NMJs) by the neurally secreted synaptic organizer Ce-Punctin/MADD-4, which also activates the transmembrane netrin receptor DCC. Those cooperatively recruit the FARP and CASK orthologues that localize α7-like-AChRs at cholinergic NMJs through physical interactions. Therefore, SDN-1 stands at the core of the cholinergic synapse organization by bridging the extracellular synaptic determinants to the intracellular synaptic scaffold that controls the postsynaptic receptor content.

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Molecular Architecture of Genetically-Tractable GABA Synapses in C. elegans

Cited by 18 publications

References 70 publications

The Evolutionary Assembly of Neuronal Machinery

The Evolutionary Assembly of Neuronal Machinery

Molecular topography of an entire nervous system

The HSPG syndecan is a core organizer of cholinergic synapses

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