scholarly journals Electrical synaptic transmission requires a postsynaptic scaffolding protein

2020 ◽  
Author(s):  
Abagael M. Lasseigne ◽  
Fabio A. Echeverry ◽  
Sundas Ijaz ◽  
Jennifer Carlisle Michel ◽  
E. Anne Martin ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Gap Junctions ◽  
Functional Organization ◽  
Scaffolding Protein ◽  
Scaffolding Proteins ◽  
Electrical Transmission ◽  
Critical Function ◽  
Electrical Synapses ◽  
Intercellular Channels ◽  
Chemical Synapses

SUMMARYElectrical synaptic transmission relies on neuronal gap junctions containing channels constructed by Connexins. While at chemical synapses neurotransmitter-gated ion channels are critically supported by scaffolding proteins, it is unknown if channels at electrical synapses require similar scaffold support. Here we investigated the functional relationship between neuronal Connexins and Zonula Occludens 1 (ZO1), an intracellular scaffolding protein localized to electrical synapses. Using model electrical synapses in zebrafish Mauthner cells, we demonstrated that ZO1 is required for robust synaptic Connexin localization, but Connexins are dispensable for ZO1 localization. Disrupting this hierarchical ZO1/Connexin relationship abolishes electrical transmission and disrupts Mauthner-cell-initiated escape responses. We found that ZO1 is asymmetrically localized exclusively postsynaptically at neuronal contacts where it functions to assemble intercellular channels. Thus, forming functional neuronal gap junctions requires a postsynaptic scaffolding protein. The critical function of a scaffolding molecule reveals an unanticipated complexity of molecular and functional organization at electrical synapses.

scholarly journals Electrical synaptic transmission requires a postsynaptic scaffolding protein

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Abagael M Lasseigne ◽  
Fabio A Echeverry ◽  
Sundas Ijaz ◽  
Jennifer Carlisle Michel ◽  
E Anne Martin ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Gap Junctions ◽  
Functional Organization ◽  
Scaffolding Protein ◽  
Scaffolding Proteins ◽  
Electrical Transmission ◽  
Critical Function ◽  
Electrical Synapses ◽  
Intercellular Channels ◽  
Chemical Synapses

Electrical synaptic transmission relies on neuronal gap junctions containing channels constructed by Connexins. While at chemical synapses neurotransmitter-gated ion channels are critically supported by scaffolding proteins, it is unknown if channels at electrical synapses require similar scaffold support. Here, we investigated the functional relationship between neuronal Connexins and Zonula Occludens 1 (ZO1), an intracellular scaffolding protein localized to electrical synapses. Using model electrical synapses in zebrafish Mauthner cells, we demonstrated that ZO1 is required for robust synaptic Connexin localization, but Connexins are dispensable for ZO1 localization. Disrupting this hierarchical ZO1/Connexin relationship abolishes electrical transmission and disrupts Mauthner cell-initiated escape responses. We found that ZO1 is asymmetrically localized exclusively postsynaptically at neuronal contacts where it functions to assemble intercellular channels. Thus, forming functional neuronal gap junctions requires a postsynaptic scaffolding protein. The critical function of a scaffolding molecule reveals an unanticipated complexity of molecular and functional organization at electrical synapses.

scholarly journals Electrical synaptic transmission in developing zebrafish: properties and molecular composition of gap junctions at a central auditory synapse

2014 ◽  
Vol 112 (9) ◽  
pp. 2102-2113 ◽  
Author(s):  
Cong Yao ◽  
Kimberly G. Vanderpool ◽  
Matthew Delfiner ◽  
Vanessa Eddy ◽  
Alexander G. Lucaci ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Gap Junctions ◽  
Developmental Stages ◽  
Neural Function ◽  
Electrical Transmission ◽  
Electrical Synapses ◽  
Connexin 36 ◽  
Auditory Responses ◽  
Electrophysiological Recordings ◽  
Chemical Synapses

In contrast to the knowledge of chemical synapses, little is known regarding the properties of gap junction-mediated electrical synapses in developing zebrafish, which provide a valuable model to study neural function at the systems level. Identifiable “mixed” (electrical and chemical) auditory synaptic contacts known as “club endings” on Mauthner cells (2 large reticulospinal neurons involved in tail-flip escape responses) allow exploration of electrical transmission in fish. Here, we show that paralleling the development of auditory responses, electrical synapses at these contacts become anatomically identifiable at day 3 postfertilization, reaching a number of ∼6 between days 4 and 9. Furthermore, each terminal contains ∼18 gap junctions, representing between 2,000 and 3,000 connexon channels formed by the teleost homologs of mammalian connexin 36. Electrophysiological recordings revealed that gap junctions at each of these contacts are functional and that synaptic transmission has properties that are comparable with those of adult fish. Thus a surprisingly small number of mixed synapses are responsible for the acquisition of auditory responses by the Mauthner cells, and these are likely sufficient to support escape behaviors at early developmental stages.

Histaminergic synaptic transmission in the cerebral ganglion of Aplysia

1985 ◽  
Vol 53 (4) ◽  
pp. 1016-1037 ◽  
Author(s):  
R. E. McCaman ◽  
D. Weinreich
Keyword(s):  
Action Potential ◽  
Synaptic Transmission ◽  
Voltage Clamp ◽  
Cerebral Ganglion ◽  
Major Influence ◽  
Electrical Synapses ◽  
Postsynaptic Potentials ◽  
Synaptic Potentials ◽  
Chemical Synapses ◽  
Synaptic Responses

Standard intracellular stimulating and recording techniques including voltage-clamp were used to analyze the synaptic responses mediated by two identifiable histamine-containing neurons (HCNs), designated C2 neurons, located in bilaterally symmetric clusters of the isolated cerebral ganglion of Aplysia california. Activation of each C2 induced unitary chemically mediated synaptic potentials in over 15 identified ipsilateral follower neurons. Several additional followers were connected to the HCNs by nonrectifying electrical synapses. Most of the follower neurons examined received only chemical synapses from the C2s. Some of the followers were reciprocally connected with each other through nonrectifying electrical synapses. A single C2 action potential can evoke six distinctive types of chemically mediated postsynaptic potentials (PSPs) in different follower neurons. Most of the PSPs have been shown to be multicomponent, i.e., they are comprised of various combinations of individual fast (less than or equal to 150 ms), slow (1-2 s), and very slow (greater than or equal to 4 s) depolarizing and hyperpolarizing components. The combination of these components produces PSPs of varying complexity, from simple monophasic responses such as the frequently observed slow excitatory PSPs and slow inhibitory PSPs to responses consisting of two to three components such as fast excitatory, slow inhibitory PSPs or fast inhibitory, slow excitatory PSPs. All of the multicomponent PSPs appear to be mediated through monosynaptic connections from the C2, as determined by various electrophysiological criteria. The slow and very slow synaptic components of the multicomponent PSPs were markedly potentiated in amplitude and duration after repetitive C2 activation. This property of the slow components permits the slower PSPs to exert a major influence on the excitability and integrative properties of the follower neurons.

Steps in the development of chemical and electrical synapses by pairs of identified leech neurons in culture

1989 ◽  
Vol 236 (1284) ◽  
pp. 253-268 ◽  
Keyword(s):  
Synaptic Transmission ◽  
Electrical Coupling ◽  
The Other ◽  
Enzyme Treatment ◽  
Sensory Cells ◽  
Electrical Transmission ◽  
Retzius Cells ◽  
Chemical Synapses ◽  
P Cells ◽  
Chemical Transmission

Experiments have been made to follow the development of chemical and electrical transmission between pairs of leech neurons in culture. 1. The cell bodies of identified neurons were isolated from the CNS by suction after mild enzyme treatment, together with a length of the initial segment (or ‘stump’). The neurons tested were Retzius cells (R), annulus erector motoneurons (AE), Anterior pagoda cells (AP) and pressure sensory cells (P). Pairs of cells were placed together in various configurations, with different sites on their surfaces making contact. 2. When pairs of Retzius cells were apposed with their stumps touching, serotonergic, chemically mediated synaptic transmission became apparent before electrical transmission. By 2.5 h impulses in either of the two Retzius cells produced hyperpolarizing inhibitory potentials in the other. These potentials were reversed by raised intracellular CI and showed clear facilitation. The strength of chemical transmission between Retzius cells increased over the next 72 h. 3. After chemical transmission had been established, weak non-recti­fying electrical transmission became apparent between Retzius cells at about 24–72 h. By 4 days coupling became stronger and tended to obscure chemically evoked synaptic potentials. 4. When pairs of Retzius cells were aligned in culture with the tip of one cell stump touching the soma of the other, chemical transmission also developed rapidly. Transmission was, however, in one direction, from stump to soma. At later stages non-rectifying electrical coupling devel­oped as with stump-stump configuration. With the cell bodies of two Retzius cells apposed, electrical coupling developed after several days, before chemical transmission could be observed. 5. When Retzius and P cells were cultured with their stumps in con­tact, inhibitory chemical synaptic transmission developed within 24 h. Transmission was always in one direction, from Retzius to P cell. Electrical coupling of Retzius and P cells never occurred whatever the spatial relations of the cells to one another. 6. Annulus erector motoneurons, which contain ACh and a peptide resembling FMRFamide, first developed electrical coupling when the two stumps were in contact and then, later, bi-directional chemical transmission. Anterior Pagoda pairs placed stump-to-stump showed electrical connections. 7. Electronmicrographs revealed the presence of synaptic structures within24 h after Retzius-Retzius, Retzius-P or AE–AE stumps were apposed. 8. The specificity of connections between cultured cells was similar to that observed in earlier experiments. A marked difference was in the speed and reliability with which chemical synapses developed when stumps were in contact. The results show that the tip of a neuron represents a preferential site for the formation of chemical synapses.

scholarly journals The Roles of Calmodulin and CaMKII in Cx36 Plasticity

2021 ◽  
Vol 22 (9) ◽  
pp. 4473
Author(s):  
Georg R. Zoidl ◽  
David C. Spray
Keyword(s):  
Synaptic Transmission ◽  
Gap Junctions ◽  
Gap Junction ◽  
Network Activity ◽  
Adaptive Plasticity ◽  
Electrical Synapses ◽  
Connexin 36 ◽  
Neuronal Network Activity ◽  
Junction Protein ◽  
Gap Junction Protein

Anatomical and electrophysiological evidence that gap junctions and electrical coupling occur between neurons was initially confined to invertebrates and nonmammals and was thought to be a primitive form of synaptic transmission. More recent studies revealed that electrical communication is common in the mammalian central nervous system (CNS), often coexisting with chemical synaptic transmission. The subsequent progress indicated that electrical synapses formed by the gap junction protein connexin-36 (Cx36) and its paralogs in nonmammals constitute vital elements in mammalian and fish synaptic circuitry. They govern the collective activity of ensembles of coupled neurons, and Cx36 gap junctions endow them with enormous adaptive plasticity, like that seen at chemical synapses. Moreover, they orchestrate the synchronized neuronal network activity and rhythmic oscillations that underlie the fundamental integrative processes, such as memory and learning. Here, we review the available mechanistic evidence and models that argue for the essential roles of calcium, calmodulin, and the Ca2+/calmodulin-dependent protein kinase II in integrating calcium signals to modulate the strength of electrical synapses through interactions with the gap junction protein Cx36.

scholarly journals Shank3 mutations impair electrical synapse scaffolding and transmission in mouse brain

2021 ◽  
Author(s):  
Jonathan Lautz ◽  
Zhiyi Zhu ◽  
Haley Speed ◽  
Stephen E.P. Smith ◽  
John P Welsh
Keyword(s):  
Intellectual Disability ◽  
Synaptic Transmission ◽  
Glutamate Receptors ◽  
Mouse Brain ◽  
Inferior Olive ◽  
Postsynaptic Density ◽  
Electrical Synapse ◽  
Electrical Synapses ◽  
Protein Scaffold ◽  
Intercellular Channels

Shank3 mutations contribute to intellectual disability. Because SHANK3 is a protein scaffold that helps organize the multiprotein network of the glutamatergic postsynaptic density (PSD), alterations in chemical synaptic transmission are implicated. Electrical synaptic transmission is a second form of synaptic transmission, enabled by intercellular channels comprised of connexin36 that support direct electrical communication among neurons, electrical brain rhythms, and neurocognitive states. Using multiplex proteomics, we report that two autism-related mutations of mouse Shank3 disrupt the glutamatergic PSD differently, but have in common the disruption of an association between NMDA-type glutamate-receptors (NMDARs) and connexin36. Mutation of Shank3 exons 13-16 most robustly dissociated connexin36 from NMDARs while impairing electrical synaptic transmission and the synchrony of an electrical rhythm in mouse inferior olive. We suggest that electrical synapses are a component of an "extended PSD" sensitive to Shank3 mutations that produce intellectual disability, at least in part, by impairing electrical synaptic transmission.

scholarly journals Scaffolding proteins guide the evolution of algal light harvesting antennas

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Harry W. Rathbone ◽  
Katharine A. Michie ◽  
Michael J. Landsberg ◽  
Beverley R. Green ◽  
Paul M. G. Curmi
Keyword(s):  
Hydrophobic Surface ◽  
Scaffolding Protein ◽  
Secondary Endosymbiosis ◽  
Scaffolding Proteins ◽  
Α Subunit ◽  
Binding Partner ◽  
Photosynthetic Organisms ◽  
New Family ◽  
Red Algal ◽  
Multiple Copies

AbstractPhotosynthetic organisms have developed diverse antennas composed of chromophorylated proteins to increase photon capture. Cryptophyte algae acquired their photosynthetic organelles (plastids) from a red alga by secondary endosymbiosis. Cryptophytes lost the primary red algal antenna, the red algal phycobilisome, replacing it with a unique antenna composed of αβ protomers, where the β subunit originates from the red algal phycobilisome. The origin of the cryptophyte antenna, particularly the unique α subunit, is unknown. Here we show that the cryptophyte antenna evolved from a complex between a red algal scaffolding protein and phycoerythrin β. Published cryo-EM maps for two red algal phycobilisomes contain clusters of unmodelled density homologous to the cryptophyte-αβ protomer. We modelled these densities, identifying a new family of scaffolding proteins related to red algal phycobilisome linker proteins that possess multiple copies of a cryptophyte-α-like domain. These domains bind to, and stabilise, a conserved hydrophobic surface on phycoerythrin β, which is the same binding site for its primary partner in the red algal phycobilisome, phycoerythrin α. We propose that after endosymbiosis these scaffolding proteins outcompeted the primary binding partner of phycoerythrin β, resulting in the demise of the red algal phycobilisome and emergence of the cryptophyte antenna.

scholarly journals A Peptide-Nucleic Acid Targeting miR-335-5p Enhances Expression of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gene with the Possible Involvement of the CFTR Scaffolding Protein NHERF1

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 117
Author(s):  
Anna Tamanini ◽  
Enrica Fabbri ◽  
Tiziana Jakova ◽  
Jessica Gasparello ◽  
Alex Manicardi ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Nucleic Acid ◽  
Peptide Nucleic Acid ◽  
Stop Codon ◽  
Scaffolding Protein ◽  
Cftr Gene ◽  
Scaffolding Proteins ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Cystic Fibrosis Transmembrane

(1) Background: Up-regulation of the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) might be of great relevance for the development of therapeutic protocols for cystic fibrosis (CF). MicroRNAs are deeply involved in the regulation of CFTR and scaffolding proteins (such as NHERF1, NHERF2 and Ezrin). (2) Methods: Content of miRNAs and mRNAs was analyzed by RT-qPCR, while the CFTR and NHERF1 production was analyzed by Western blotting. (3) Results: The results here described show that the CFTR scaffolding protein NHERF1 can be up-regulated in bronchial epithelial Calu-3 cells by a peptide-nucleic acid (PNA) targeting miR-335-5p, predicted to bind to the 3′-UTR sequence of the NHERF1 mRNA. Treatment of Calu-3 cells with this PNA (R8-PNA-a335) causes also up-regulation of CFTR. (4) Conclusions: We propose miR-335-5p targeting as a strategy to increase CFTR. While the efficiency of PNA-based targeting of miR-335-5p should be verified as a therapeutic strategy in CF caused by stop-codon mutation of the CFTR gene, this approach might give appreciable results in CF cells carrying other mutations impairing the processing or stability of CFTR protein, supporting its application in personalized therapy for precision medicine.

Effects of Time Delay on Burst Synchronization Transition of Neuronal Networks

2018 ◽  
Vol 28 (12) ◽  
pp. 1850143 ◽  
Author(s):  
Xiaojuan Sun ◽  
Tianshu Xue
Keyword(s):  
Time Delay ◽  
Neuronal Network ◽  
Coupling Strength ◽  
Neuronal Networks ◽  
The Other ◽  
Electrical Synapses ◽  
Synchronization Transition ◽  
Burst Synchronization ◽  
Chemical Synapses ◽  
Bursting Activity

In this paper, we focus on investigating the effects of time delay on burst synchronization transitions of a neuronal network which is locally modeled by Hindmarsh–Rose neurons. Here, neurons inside the neuronal network are connected through electrical synapses or chemical synapses. With the numerical results, it is revealed that burst synchronization transitions of both electrically and chemically coupled neuronal networks could be induced by time delay just when the coupling strength is large enough. Meanwhile, it is found that, in electrically and excitatory chemically coupled neuronal networks, burst synchronization transitions are observed through change of spiking number per burst when coupling strength is large enough; while in inhibitory chemically coupled neuronal network, burst synchronization transitions are observed for large enough coupling strength through changing fold-Hopf bursting activity to fold-homoclinic bursting activity and vice versa. Namely, two types of burst synchronization transitions are observed. One type of burst synchronization transitions occurs through change of spiking numbers per burst and the other type of burst synchronization transition occurs through change of bursting types.

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