A Syd-1 homologue regulates pre- and postsynaptic maturation in <i>Drosophila</i>

Owald, David; Fouquet, Wernher; Schmidt, Manuela; Wichmann, Carolin; Mertel, Sara; Depner, Harald; Christiansen, Frauke; Zube, Christina; Quentin, Christine; Körner, Jorg; Urlaub, Henning; Mechtler, Karl; Sigrist, Stephan J.

doi:10.1083/jcb.200908055

Cited by 175 publications

(260 citation statements)

References 49 publications

(118 reference statements)

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“…1a) and Liprin-α (Syd-2) promote presynaptic assembly 5,[15][16][17][18] . When we expressed Nlg1∆Cyto in a Liprin-α mutant background, NMJ terminals still showed severe under-growth compared to those in the Liprin-α mutant background alone (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…To test whether Syd-1 genetically interacts with Nrx-1 or Nlg1, we constructed the respective double mutants. NMJ size is reduced in Nlg1, Nrx-1 and Syd-1 single mutants, as well as in Liprin-α single mutants 5,11,12,18 . As expected, all these single mutants showed significantly reduced bouton numbers as compared to controls (Fig.…”

Section: Similar Synaptic Phenotypes Of Syd-1 Nrx-1 and Nlg1mentioning

confidence: 98%

“…Later PSD maturation is marked by the incorporation of GluRIIB-containing receptor complexes 6 . Synapse assembly is concluded at presynaptic active zones by the incorporation of the active zone scaffold component Bruchpilot (BRP) 5 .Coordinating synapse assembly requires signaling across the synaptic cleft, which separates pre-from postsynaptic membranes. Transsynaptic cell adhesion molecules are obvious candidates for coupling active zone and PSD assembly.…”

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confidence: 99%

“…In vivo imaging has shown that presynaptic Syd-1 and Liprin-α clusters initiate active zone formation 5 . On the postsynaptic side, initial PSD growth depends on incorporation of a glutamate receptor (GluR) containing the GluRIIA subunit.…”

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Cooperation of Syd-1 with Neurexin synchronizes pre- with postsynaptic assembly

et al. 2012

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Understanding the process of synapse assembly in molecular and cell-biological detail is a prerequisite for understanding neural circuit development and activity-mediated remodeling, and thus is important for unraveling learning and memory processes (structural plasticity) [1][2][3] . Functional chemical synapses are characterized by two apposed compartments that must be coestablished with high spatiotemporal precision: the presynaptic active zone, where regulated and rapid fusion of neurotransmitter-filled synaptic vesicles takes place, and the postsynaptic density (PSD), which embeds neurotransmitter receptors.Glutamatergic neuromuscular junction (NMJ) terminals of Drosophila larvae grow to meet the requirements of the growing muscle fibers, a process in which new synapses are continuously added 4 (where a synapse is defined as a single active zone opposed by a single PSD 1 ). In vivo imaging has shown that presynaptic Syd-1 and Liprin-α clusters initiate active zone formation 5 . On the postsynaptic side, initial PSD growth depends on incorporation of a glutamate receptor (GluR) containing the GluRIIA subunit. Later PSD maturation is marked by the incorporation of GluRIIB-containing receptor complexes 6 . Synapse assembly is concluded at presynaptic active zones by the incorporation of the active zone scaffold component Bruchpilot (BRP) 5 .Coordinating synapse assembly requires signaling across the synaptic cleft, which separates pre-from postsynaptic membranes. Transsynaptic cell adhesion molecules are obvious candidates for coupling active zone and PSD assembly. In vitro, the Neurexin-Neuroligin (Nrx-Nlg) complex can mediate the trans-synaptic signaling required for synapse assembly 7,8 . How this signaling axis integrates with the additional assembly machinery, however, has remained largely unclear.Here, we provide evidence of a dual role for Syd-1 in early assembly of NMJ synapses. It retains Liprin-α clusters at active zones and is important for clustering of presynaptic Nrx-1, likely through a direct and PDZ-domain-dependent interaction. Consequently, Syd-1 is also needed for clustering of postsynaptic Nlg1, which organizes postsynaptic assembly. Coincident action of Syd-1 with Nrx-1-Nlg1 appears to allow active zone scaffolds to pass through an initial, still fragile assembly phase. We suggest that binding between Syd-1 and Nrx-1-Nlg1 is a means to coordinate pre-with postsynaptic assembly. Our study shows an example of how coincident action of a presynaptic active zone scaffold protein and a trans-synaptic cell adhesion protein module can spatiotemporally orchestrate synapse assembly. RESULTSInitially described in cell culture systems (for a review, see ref. 9), interaction between mammalian presynaptic Nrx proteins and postsynaptic Nlg molecules was proposed to be important for proper synapse assembly. However, genetic ablation of three Nlg (Nlgn) genes in mice 10 does not result in a substantial structural phenotype, potentially reflecting a strong capacity for compensatory processes in vivo.Nonethe...

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Section: Resultsmentioning

confidence: 99%

Section: Similar Synaptic Phenotypes Of Syd-1 Nrx-1 and Nlg1mentioning

confidence: 98%

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confidence: 99%

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confidence: 99%

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Cooperation of Syd-1 with Neurexin synchronizes pre- with postsynaptic assembly

et al. 2012

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Regulation of synaptic release‐site Ca²⁺ channel coupling as a mechanism to control release probability and short‐term plasticity

2018

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Synaptic transmission relies on the rapid fusion of neurotransmitter-containing synaptic vesicles (SVs), which happens in response to action potential (AP)-induced Ca influx at active zones (AZs). A highly conserved molecular machinery cooperates at SV-release sites to mediate SV plasma membrane attachment and maturation, Ca sensing, and membrane fusion. Despite this high degree of conservation, synapses - even within the same organism, organ or neuron - are highly diverse regarding the probability of APs to trigger SV fusion. Additionally, repetitive activation can lead to either strengthening or weakening of transmission. In this review, we discuss mechanisms controlling release probability and this short-term plasticity. We argue that an important layer of control is exerted by evolutionarily conserved AZ scaffolding proteins, which determine the coupling distance between SV fusion sites and voltage-gated Ca channels (VGCC) and, thereby, shape synapse-specific input/output behaviors. We propose that AZ-scaffold modifications may occur to adapt the coupling distance during synapse maturation and plastic regulation of synapse strength.

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Aging Drosophila melanogaster display altered pre‐ and postsynaptic ultrastructure at adult neuromuscular junctions

Wagner

Laugks

Heckmann

et al. 2015

J of Comparative Neurology

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Although age-related changes in synaptic plasticity are an important focus within neuroscience, little is known about ultrastructural changes of synaptic morphology during aging. Here we report how aging affects synaptic ultrastructure by using fluorescence and electron microscopy at the adult Drosophila neuromuscular junction (NMJ) of ventral abdominal muscles. Mainly four striking morphological changes of aging NMJs were revealed. 1) Bouton size increases with proportionally rising number of active zones (AZs). 2) Synaptic vesicle density at AZs is increased in old flies. 3) Late endosomes, cisternae, and multivesicular bodies accumulate in the presynaptic terminal, and vesicles accumulate between membranes of the terminal bouton and the subsynaptic reticulum. 4) The electron-dense pre- and postsynaptic apposition is expanded in aging NMJs, which is accompanied by an expansion of the postsynaptic glutamate receptor fields. These findings suggest that aging is possibly accompanied by impaired synaptic vesicle release and recycling and a potentially compensatory expansion of AZs and postsynaptic densities.

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A Syd-1 homologue regulates pre- and postsynaptic maturation in Drosophila

Abstract: A proteomics approach identifies Drosophila Syd-1 as a Bruchpilot binding partner that controls maturation on both sides of the neuromuscular junction.

Cited by 175 publications

References 49 publications

Cooperation of Syd-1 with Neurexin synchronizes pre- with postsynaptic assembly

Cooperation of Syd-1 with Neurexin synchronizes pre- with postsynaptic assembly

Regulation of synaptic release‐site Ca²⁺ channel coupling as a mechanism to control release probability and short‐term plasticity

Aging Drosophila melanogaster display altered pre‐ and postsynaptic ultrastructure at adult neuromuscular junctions

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A Syd-1 homologue regulates pre- and postsynaptic maturation in Drosophila

Abstract: A proteomics approach identifies Drosophila Syd-1 as a Bruchpilot binding partner that controls maturation on both sides of the neuromuscular junction.

Cited by 175 publications

References 49 publications

Cooperation of Syd-1 with Neurexin synchronizes pre- with postsynaptic assembly

Cooperation of Syd-1 with Neurexin synchronizes pre- with postsynaptic assembly

Regulation of synaptic release‐site Ca2+ channel coupling as a mechanism to control release probability and short‐term plasticity

Aging Drosophila melanogaster display altered pre‐ and postsynaptic ultrastructure at adult neuromuscular junctions

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Regulation of synaptic release‐site Ca²⁺ channel coupling as a mechanism to control release probability and short‐term plasticity