Clathrin packets move in slow axonal transport and deliver functional payloads to synapses

Ganguly, Archan; Sharma, Rohan; Boyer, Nicholas P.; Wernert, Florian; Phan, Sébastien; Boassa, Daniela; Parra, Leonardo A.; Das, Utpal; Caillol, Ghislaine; Han, Xuemei; Yates, John R.; Ellisman, Mark H.; Leterrier, Christophe; Roy, Subhojit

doi:10.1016/j.neuron.2021.08.016

Cited by 22 publications

(8 citation statements)

References 111 publications

(153 reference statements)

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“…However, when pHluorin is exposed to the extracellular neutral pH, it becomes ~100 times more fluorescent 34 (Figure 1A). We expressed LGI1-pH in primary excitatory hippocampal neurons that were co-cultured with astrocytes, a system that optimizes the optical access to single synapses and allows robustly quantifying dynamic changes in fluorescence in individual nerve terminals [35][36][37] . Selective expression in excitatory neurons was achieved by using the CaMKII promoter, as described previously 38 .…”

Section: Resultsmentioning

confidence: 99%

Activity-driven synaptic translocation of LGI1 controls excitatory neurotransmission

Cuhadar

Calzado-Reyes

Pascual-Caro

et al. 2022

Preprint

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The fine control of synaptic function requires robust trans-synaptic molecular interactions. However, it remains poorly understood how the landscape of trans-synaptic bridges dynamically remodels to reflect functional states of the synapse. Here we developed novel optical tools to visualize in firing synapses the molecular behavior of a particular secreted trans-synaptic protein, LGI1, and its presynaptic receptor, ADAM23, and discovered that neuronal activity acutely rearranges the abundance of these proteins at the synaptic cleft. Surprisingly, LGI1 in synapses was not secreted, as described elsewhere, but exo- and endocytosed through its interaction with ADAM23. Activity-driven translocation of LGI1 facilitated the formation of trans-synaptic connections proportionally to the history of activity of the synapse, modulating excitatory transmission correlatively to synaptic firing rates. Thus, our findings reveal that LGI1 abundance at the synaptic cleft can be acutely remodeled and serves as critical point of activity-dependent control of synaptic function.

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Section: Resultsmentioning

confidence: 99%

Activity-driven synaptic translocation of LGI1 controls excitatory neurotransmission

Cuhadar

Calzado-Reyes

Pascual-Caro

et al. 2022

Preprint

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“…, 2014 ; Reshetniak et al. , 2020 ), or the axonal transport and synaptic retention of clathrin “packets” ( Ganguly et al. , 2021 ).…”

Section: Discussionmentioning

confidence: 99%

An approach for quantitative mapping of synaptic periactive zone architecture and organization

Signore

Mitzner

Fai

et al. 2023

MBoC

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Following exocytosis at active zones, synaptic vesicle membranes and membrane-bound proteins must be recycled. The endocytic machinery that drives this recycling accumulates in the periactive zone (PAZ), a region of the synapse adjacent to active zones, but the organization of this machinery within the PAZ, and how PAZ composition relates to active zone release properties remains unknown. The PAZ is also enriched for cell adhesion proteins, but their function at these sites is poorly understood. Here, using Airyscan and STED imaging of Drosophila synapses, we develop a quantitative framework describing the organization and ultrastructure of the PAZ. Different endocytic proteins localize to distinct regions of the PAZ, suggesting that sub-domains are specialized for distinct biochemical activities, stages of membrane remodeling, or synaptic functions. We find that the accumulation and distribution of endocytic but not adhesion PAZ proteins correlate with the abundance of the scaffolding protein Bruchpilot at active zones - a structural correlate of release probability. These data suggest that endocytic and exocytic activities are spatially correlated. Taken together, our results identify novel relationships between the exocytic and endocytic apparatus at the synapse and provide a new conceptual framework to quantify synaptic architecture.

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“…Historically, the spectrin scaffold is considered as a skeletal integrator [45], capable of organizing the logistic distribution of a plethora of binding partners, cytoskeletal and membrane trafficking events. We previously reported reduced AP2-dependent endocytic events in correspondence of dense spectrin regions induced by osmotic fluctuations [13]; similarly, in neurons clathrin “packets” associate with the spectrin periodic scaffold along the axons, but never fused to the adjacent plasma membrane, suggesting the existence of a membrane fusion barrier in presence of a dense spectrin array [46]. Recent proteomic investigations identified proteins specifically associated with the periodic scaffold and not with the extended meshwork [47]: in particular the structural WD-repeat containing proteins (i.e., coronins), transmembrane channels and receptors (i.e., potassium and sodium ion channels, GPCRs, RTKs), and the signaling molecule CAMK IIβ.…”

Section: Discussionmentioning

confidence: 99%

Mechanically induced topological transition of spectrin regulates its distribution in the mammalian cortex

Ghisleni

Bonilla-Quintana

Crestani

et al. 2023

Preprint

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The cell cortex is a dynamic assembly formed by the plasma membrane and the underlying cytoskeleton. As the main determinant of cell shape, the cortex ensures its integrity during passive deformation or active response by adapting cytoskeleton topologies with poorly understood mechanisms. The spectrin meshwork ensures such adaptation in erythrocytes and neurons by adopting dramatically different organizations. Erythrocytes rely on triangular-like lattices of spectrin tetramers, which in neurons are organized in parallel and periodic arrays. Since spectrin is ubiquitously expressed, we exploited Expansion Microscopy to discover that these two distinct topologies can co-exist in other mammalian cells such as fibroblasts. We show through biophysical measurements and computational modeling that spectrin provides coverage of the cortex and, with the intervention of actomyosin, erythroid-like lattices can dynamically transition into condensates that resemble neuron-like periodic arrays fenced by actin stress fibers. Spectrin condensates experience lower mechanical stress and turnover despite displaying an extension close to the contour length of the tetramer. Our study sheds light on the adaptive properties of spectrin, which ensures protection of the cortex by undergoing mechanically induced topological transitions.

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Clathrin packets move in slow axonal transport and deliver functional payloads to synapses

Cited by 22 publications

References 111 publications

Activity-driven synaptic translocation of LGI1 controls excitatory neurotransmission

Activity-driven synaptic translocation of LGI1 controls excitatory neurotransmission

An approach for quantitative mapping of synaptic periactive zone architecture and organization

Mechanically induced topological transition of spectrin regulates its distribution in the mammalian cortex

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