scholarly journals Scribble Interacts with β-Catenin to Localize Synaptic Vesicles to Synapses

2009 ◽  
Vol 20 (14) ◽  
pp. 3390-3400 ◽  
Author(s):  
Yu Sun ◽  
Mytyl Aiga ◽  
Eileen Yoshida ◽  
Patrick O. Humbert ◽  
Shernaz X. Bamji
Keyword(s):  
Rna Interference ◽  
Active Zone ◽  
Synaptic Vesicles ◽  
Molecular Mechanisms ◽  
Primary Neurons ◽  
Vesicle Recycling ◽  
Presynaptic Active Zone ◽  
Presynaptic Assembly ◽  
Diffuse Distribution

An understanding of how synaptic vesicles are recruited to and maintained at presynaptic compartments is required to discern the molecular mechanisms underlying presynaptic assembly and plasticity. We have previously demonstrated that cadherin–β-catenin complexes cluster synaptic vesicles at presynaptic sites. Here we show that scribble interacts with the cadherin–β-catenin complex to coordinate vesicle localization. Scribble and β-catenin are colocalized at synapses and can be coimmunoprecipitated from neuronal lysates, indicating an interaction between scribble and β-catenin at the synapse. Using an RNA interference approach, we demonstrate that scribble is important for the clustering of synaptic vesicles at synapses. Indeed, in scribble knockdown cells, there is a diffuse distribution of synaptic vesicles along the axon, and a deficit in vesicle recycling. Despite this, synapse number and the distribution of the presynaptic active zone protein, bassoon, remain unchanged. These effects largely phenocopy those observed after ablation of β-catenin. In addition, we show that loss of β-catenin disrupts scribble localization in primary neurons but that the localization of β-catenin is not dependent on scribble. Our data supports a model by which scribble functions downstream of β-catenin to cluster synaptic vesicles at developing synapses.

scholarly journals The proteome of the presynaptic active zone: from docked synaptic vesicles to adhesion molecules and maxi-channels

2009 ◽  
Vol 108 (3) ◽  
pp. 662-675 ◽  
Author(s):  
Marco Morciano ◽  
Tobias Beckhaus ◽  
Michael Karas ◽  
Herbert Zimmermann ◽  
Walter Volknandt
Keyword(s):  
Adhesion Molecules ◽  
Active Zone ◽  
Synaptic Vesicles ◽  
Presynaptic Active Zone

scholarly journals Colocalization of synapsin and actin during synaptic vesicle recycling

2003 ◽  
Vol 161 (4) ◽  
pp. 737-747 ◽  
Author(s):  
Ona Bloom ◽  
Emma Evergren ◽  
Nikolay Tomilin ◽  
Ole Kjaerulff ◽  
Peter Löw ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Synaptic Vesicle ◽  
Active Zone ◽  
Synaptic Vesicles ◽  
Synaptic Activity ◽  
Immunogold Electron Microscopy ◽  
Synaptic Vesicle Recycling ◽  
Vesicle Recycling ◽  
Reserve Pool ◽  
Giant Synapse

It has been hypothesized that in the mature nerve terminal, interactions between synapsin and actin regulate the clustering of synaptic vesicles and the availability of vesicles for release during synaptic activity. Here, we have used immunogold electron microscopy to examine the subcellular localization of actin and synapsin in the giant synapse in lamprey at different states of synaptic activity. In agreement with earlier observations, in synapses at rest, synapsin immunoreactivity was preferentially localized to a portion of the vesicle cluster distal to the active zone. During synaptic activity, however, synapsin was detected in the pool of vesicles proximal to the active zone. In addition, actin and synapsin were found colocalized in a dynamic filamentous cytomatrix at the sites of synaptic vesicle recycling, endocytic zones. Synapsin immunolabeling was not associated with clathrin-coated intermediates but was found on vesicles that appeared to be recycling back to the cluster. Disruption of synapsin function by microinjection of antisynapsin antibodies resulted in a prominent reduction of the cytomatrix at endocytic zones of active synapses. Our data suggest that in addition to its known function in clustering of vesicles in the reserve pool, synapsin migrates from the synaptic vesicle cluster and participates in the organization of the actin-rich cytomatrix in the endocytic zone during synaptic activity.

scholarly journals Critical role for Piccolo in Synaptic Vesicle Retrieval

2018 ◽  
Author(s):  
Frauke Ackermann ◽  
Kay O. Schink ◽  
Christine Bruns ◽  
Zsuzsanna Izsvák ◽  
F. Kent Hamra ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Active Zone ◽  
Synaptic Vesicles ◽  
Depressive Disorders ◽  
Critical Role ◽  
Neuronal Loss ◽  
Synaptic Function ◽  
Loss Of Function ◽  
Early Endosomes ◽  
Presynaptic Active Zone

AbstractLoss of function of the presynaptic active zone protein Piccolo has recently been linked to a devastating disease causing brain atrophy. Here, we address how Piccolo inactivation adversely affects synaptic function and thus may contributes to neuronal loss. Our analysis shows that Piccolo is critical for the activity dependent recycling and maintenance of synaptic vesicles (SVs). Specifically, we find that boutons lacking Piccolo have deficits in the Rab5/EEA1 dependent formation of early endosomes and thus the recycling of SVs. Mechanistically, impaired Rab5 function was caused by the reduced synaptic recruitment of Pra1, known to interact selectively with the zinc fingers of Piccolo. Importantly, over-expression of GTPase deficient Rab5 or the Znf1 domain of Piccolo restores the size and recycling of SV pools. These data provide a molecular link between the active zone and endosome sorting at synapses providing hints to how Piccolo contributes to both developmental and psychiatric disorders.Impact StatementThe efficient recycling of synaptic vesicle proteins is critical for the integrity and reliability of synaptic transmission. Increasingly genetic and environmental insults have been shown to affect this recycling pathway, resulting in both cognitive impairment in humans and neurodegenerative diseases, yet the underlying mechanisms are poorly understood. Here we could show that the presynaptic active zone protein Piccolo regulates efficient recycling of synaptic vesicles via Pra1 and Rab5, perhaps explaining why Piccolo loss of function contributes to Pontocerebellar Hypoplasia and major depressive disorders.

scholarly journals Neurexins regulate presynaptic GABAB-receptors at central synapses

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Fujun Luo ◽  
Alessandra Sclip ◽  
Sean Merrill ◽  
Thomas C. Südhof
Keyword(s):  
Active Zone ◽  
Neurotransmitter Release ◽  
Molecular Mechanisms ◽  
Pyramidal Neurons ◽  
Receptor Activation ◽  
Gabab Receptors ◽  
Inhibitory Synapses ◽  
Receptor Signaling ◽  
Ca1 Region ◽  
Presynaptic Active Zone

AbstractDiverse signaling complexes are precisely assembled at the presynaptic active zone for dynamic modulation of synaptic transmission and synaptic plasticity. Presynaptic GABAB-receptors nucleate critical signaling complexes regulating neurotransmitter release at most synapses. However, the molecular mechanisms underlying assembly of GABAB-receptor signaling complexes remain unclear. Here we show that neurexins are required for the localization and function of presynaptic GABAB-receptor signaling complexes. At four model synapses, excitatory calyx of Held synapses in the brainstem, excitatory and inhibitory synapses on hippocampal CA1-region pyramidal neurons, and inhibitory basket cell synapses in the cerebellum, deletion of neurexins rendered neurotransmitter release significantly less sensitive to GABAB-receptor activation. Moreover, deletion of neurexins caused a loss of GABAB-receptors from the presynaptic active zone of the calyx synapse. These findings extend the role of neurexins at the presynaptic active zone to enabling GABAB-receptor signaling, supporting the notion that neurexins function as central organizers of active zone signaling complexes.

Amyloid Precursor Protein Knockout Diminishes Synaptic Vesicle Proteins at the Presynaptic Active Zone in Mouse Brain

2014 ◽  
Vol 11 (10) ◽  
pp. 971-980 ◽  
Author(s):  
Melanie Laßek ◽  
Jens Weingarten ◽  
Amparo Acker-Palmer ◽  
Sandra Bajjalieh ◽  
Ulrike Muller ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Synaptic Vesicle ◽  
Mouse Brain ◽  
Active Zone ◽  
Precursor Protein ◽  
Presynaptic Active Zone ◽  
Vesicle Proteins

scholarly journals Ketamine Alters Functional Plasticity of Astroglia: An Implication for Antidepressant Effect

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 573
Author(s):  
Matjaž Stenovec
Keyword(s):  
Molecular Mechanisms ◽  
Neuronal Firing ◽  
Fusion Pore ◽  
Antidepressant Effect ◽  
Intracellular Camp ◽  
Lateral Habenula ◽  
Vesicle Recycling ◽  
The Central Nervous System ◽  
Inward Rectifying Potassium Channel ◽  
Antidepressant Action

Ketamine, a non-competitive N–methyl–d–aspartate receptor (NMDAR) antagonist, exerts a rapid, potent and long-lasting antidepressant effect, although the cellular and molecular mechanisms of this action are yet to be clarified. In addition to targeting neuronal NMDARs fundamental for synaptic transmission, ketamine also affects the function of astrocytes, the key homeostatic cells of the central nervous system that contribute to pathophysiology of major depressive disorder. Here, I review studies revealing that (sub)anesthetic doses of ketamine elevate intracellular cAMP concentration ([cAMP]i) in astrocytes, attenuate stimulus-evoked astrocyte calcium signaling, which regulates exocytotic secretion of gliosignaling molecules, and stabilize the vesicle fusion pore in a narrow configuration, possibly hindering cargo discharge or vesicle recycling. Next, I discuss how ketamine affects astrocyte capacity to control extracellular K+ by reducing vesicular delivery of the inward rectifying potassium channel (Kir4.1) to the plasmalemma that reduces the surface density of Kir4.1. Modified astroglial K+ buffering impacts upon neuronal firing pattern as demonstrated in lateral habenula in a rat model of depression. Finally, I highlight the discovery that ketamine rapidly redistributes cholesterol in the astrocyte plasmalemma, which may alter the flux of cholesterol to neurons. This structural modification may further modulate a host of processes that synergistically contribute to ketamine’s rapid antidepressant action.

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