scholarly journals Gap junctions: historical discoveries and new findings in the Caenorhabditiselegans nervous system

Biology Open ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. bio053983 ◽  
Author(s):  
Eugene Jennifer Jin ◽  
Seungmee Park ◽  
Xiaohui Lyu ◽  
Yishi Jin
Keyword(s):  
Nervous System ◽  
Gap Junctions ◽  
Vast Number ◽  
C Elegans ◽  
New Findings ◽  
Evolutionarily Conserved ◽  
Multiple Processes ◽  
Neuronal Tissues ◽  
Membrane Contacts ◽  
And Function

ABSTRACTGap junctions are evolutionarily conserved structures at close membrane contacts between two cells. In the nervous system, they mediate rapid, often bi-directional, transmission of signals through channels called innexins in invertebrates and connexins in vertebrates. Connectomic studies from Caenorhabditis elegans have uncovered a vast number of gap junctions present in the nervous system and non-neuronal tissues. The genome also has 25 innexin genes that are expressed in spatial and temporal dynamic pattern. Recent findings have begun to reveal novel roles of innexins in the regulation of multiple processes during formation and function of neural circuits both in normal conditions and under stress. Here, we highlight the diverse roles of gap junctions and innexins in the C. elegans nervous system. These findings contribute to fundamental understanding of gap junctions in all animals.

scholarly journals Heparan sulfate molecules mediate synapse formation and function of male mating neural circuits in C. elegans

2018 ◽  
Author(s):  
María I. Lázaro-Peña ◽  
Carlos A. Díaz-Balzac ◽  
Hannes E. Bülow ◽  
Scott W. Emmons
Keyword(s):  
Nervous System ◽  
Cell Adhesion ◽  
Neural Cell ◽  
Male Mating ◽  
Synaptic Connections ◽  
Adhesion Protein ◽  
C Elegans ◽  
Neural Cell Adhesion ◽  
Heparan Sulfates ◽  
And Function

AbstractThe nervous system regulates complex behaviors through a network of neurons interconnected by synapses. How specific synaptic connections are genetically determined is still unclear. Male mating is the most complex behavior in C. elegans. It is composed of sequential steps that are governed by more than 3,000 chemical connections. Here we show that heparan sulfates (HS) play a role in the formation and function of the male neural network. Cell-autonomous and non-autonomous 3-O sulfation by the HS modification enzyme HST-3.1/HS 3-O-sulfotransferase, localized to the HSPG glypicans LON-2/glypican and GPN-1/glypican, was specifically required for response to hermaphrodite contact during mating. Loss of 3-O sulfation resulted in the presynaptic accumulation of RAB-3, a molecule that localizes to synaptic vesicles, disrupting the formation of synapses in a component of the mating circuits. We also show that neural cell adhesion protein neurexin promotes and neural cell adhesion protein neuroligin inhibits formation of the same set of synapses in a parallel pathway. Thus, neural cell adhesion proteins and extracellular matrix components act together in the formation of synaptic connections.Author SummaryThe formation of the nervous system requires the function of several genetically-encoded proteins to form complex networks. Enzymatically-generated modifications of these proteins play a crucial role during this process. These authors analyzed the role of heparan sulfates in the process of synaptogenesis in the male tail of C. elegans. A modification of heparan sulfate is required for the formation of specific synapses between neurons by acting cell-autonomously and non-autonomously. Could it be that heparan sulfates and their diverse modifications are a component of the specification factor that neurons use to make such large numbers of connections unique?

scholarly journals Gap junctions in the C. elegans nervous system regulate ageing and lifespan

2019 ◽  
Author(s):  
Nathalie Alexandra Vladis ◽  
Katharina Elisabeth Fischer ◽  
Eva Digalaki ◽  
Daniel-Cosmin Marcu ◽  
Modestos Nakos Bimpos ◽  
...  
Keyword(s):  
Nervous System ◽  
Gap Junctions ◽  
Signal Transmission ◽  
Life Extension ◽  
C Elegans ◽  
Neuronal Communication ◽  
Age Dependent ◽  
Genes Encoding ◽  
Metabolic Signal ◽  
First Time

AbstractThe nervous system is a central regulator of longevity, but how neuronal communication interfaces with ageing pathways is not well understood. Gap junctions are key conduits that allow voltage and metabolic signal transmission across cellular networks, yet it has remained unexplored whether they play a role in regulating ageing and longevity. We show that the innexin genes encoding gap junction subunits in Caenorhabditis elegans have extensive and diverse impacts on lifespan. Loss of the neural innexin unc-9 increases longevity by a third and also strongly benefits healthspan. Unc-9 acts specifically in a glutamatergic circuit linked to mechanosensation. Absence of unc-9 depends on a functional touch-sensing machinery to regulate lifespan and alters the age-dependent decline of mechanosensory neurons. The life extension produced by removal of unc-9 requires reactive oxygen species. Our work reveals for the first time that gap junctions are important regulators of ageing and lifespan.

scholarly journals A cellular and regulatory map of the cholinergic nervous system of C. elegans

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Laura Pereira ◽  
Paschalis Kratsios ◽  
Esther Serrano-Saiz ◽  
Hila Sheftel ◽  
Avi E Mayo ◽  
...  
Keyword(s):  
Nervous System ◽  
Sexually Dimorphic ◽  
Anion Channels ◽  
Inhibitory Neurotransmitter ◽  
C Elegans ◽  
Transcriptional Regulatory ◽  
System Maps ◽  
Transcriptional Regulatory Mechanisms ◽  
And Function ◽  
Cholinergic Neurotransmitter

Nervous system maps are of critical importance for understanding how nervous systems develop and function. We systematically map here all cholinergic neuron types in the male and hermaphrodite C. elegans nervous system. We find that acetylcholine (ACh) is the most broadly used neurotransmitter and we analyze its usage relative to other neurotransmitters within the context of the entire connectome and within specific network motifs embedded in the connectome. We reveal several dynamic aspects of cholinergic neurotransmitter identity, including a sexually dimorphic glutamatergic to cholinergic neurotransmitter switch in a sex-shared interneuron. An expression pattern analysis of ACh-gated anion channels furthermore suggests that ACh may also operate very broadly as an inhibitory neurotransmitter. As a first application of this comprehensive neurotransmitter map, we identify transcriptional regulatory mechanisms that control cholinergic neurotransmitter identity and cholinergic circuit assembly.

scholarly journals Molecular topography of an entire nervous system

2020 ◽  
Author(s):  
Seth R Taylor ◽  
Gabriel Santpere ◽  
Alexis Weinreb ◽  
Alec Barrett ◽  
Molly B. Reilly ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Web Application ◽  
Gene Families ◽  
Regulatory Elements ◽  
Individual Neuron ◽  
Specific Gene ◽  
C Elegans ◽  
Underlying Mechanisms ◽  
And Function

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.

scholarly journals Him-10 Is Required for Kinetochore Structure and Function on Caenorhabditis elegans Holocentric Chromosomes

2001 ◽  
Vol 153 (6) ◽  
pp. 1227-1238 ◽  
Author(s):  
Mary Howe ◽  
Kent L. McDonald ◽  
Donna G. Albertson ◽  
Barbara J. Meyer
Keyword(s):  
Caenorhabditis Elegans ◽  
Structure And Function ◽  
Holocentric Chromosomes ◽  
Molecular Architecture ◽  
Mitotic Chromosomes ◽  
C Elegans ◽  
Meiotic Chromosomes ◽  
Evolutionarily Conserved ◽  
And Function ◽  
Chromosome Nondisjunction

Macromolecular structures called kinetochores attach and move chromosomes within the spindle during chromosome segregation. Using electron microscopy, we identified a structure on the holocentric mitotic and meiotic chromosomes of Caenorhabditis elegans that resembles the mammalian kinetochore. This structure faces the poles on mitotic chromosomes but encircles meiotic chromosomes. Worm kinetochores require the evolutionarily conserved HIM-10 protein for their structure and function. HIM-10 localizes to the kinetochores and mediates attachment of chromosomes to the spindle. Depletion of HIM-10 disrupts kinetochore structure, causes a failure of bipolar spindle attachment, and results in chromosome nondisjunction. HIM-10 is related to the Nuf2 kinetochore proteins conserved from yeast to humans. Thus, the extended kinetochores characteristic of C. elegans holocentric chromosomes provide a guide to the structure, molecular architecture, and function of conventional kinetochores.

scholarly journals Tobacco and Nervous System Development and Function—New Findings 2015–2020

2021 ◽  
Vol 11 (6) ◽  
pp. 797
Author(s):  
Wojciech Hajdusianek ◽  
Aleksandra Żórawik ◽  
Marta Waliszewska-Prosół ◽  
Rafał Poręba ◽  
Paweł Gać
Keyword(s):  
Nervous System ◽  
Human Body ◽  
Negative Impact ◽  
Human Life ◽  
Public Health Problem ◽  
Nervous System Development ◽  
Brain Morphology ◽  
Negative Effects ◽  
New Findings ◽  
And Function

Tobacco is a one of the most common addictive stimulants used by people around the world. The smoke generated during tobacco combustion is a toxic mixture of more than 5000 chemicals of which over 30 are known human carcinogens. While its negative effects on the human body are well understood, it remains a serious public health problem. One of the multiple effects of smoking is tobacco’s effect on the nervous system—its development and function. This review aims to summarize the progress made in research on the effects of tobacco on the nervous system both of the perinatal period and adults and both in animals and humans in 2015–2020. The 1245 results that corresponded to the keywords “tobacco, cigarette, nervous system, brain, morphology, function” were reviewed, of which 200 abstracts were considered significant. Most of those articles broadened the knowledge about the negative effects of smoking on the human nervous system. Tobacco has a significant negative impact on the development of nervous structures, neurotransmission and cognitive functions, and promotes the development of neurodegenerative diseases, insomnia and cerebrovascular diseases. The only exception is the protective effect of the dopaminergic system in Parkinson’s disease. In conclusion, in recent years much effort has been devoted to describing, revealing and uncovering new aspects of tobacco detrimental to human life. The nicotine contained in tobacco smoke affects the human body in a multidimensional way, including a serious impact on the broadly understood neurological health.

scholarly journals Methods for analyzing neuronal structure and activity in Caenorhabditis elegans

Genetics ◽  
2021 ◽  
Author(s):  
Scott W Emmons ◽  
Eviatar Yemini ◽  
Manuel Zimmer
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Fluorescent Probes ◽  
Synapse Formation ◽  
System Structure ◽  
Neuronal Structure ◽  
Fluorescent Reporters ◽  
C Elegans ◽  
Consistent Manner ◽  
And Function

Abstract The model research animal Caenorhabditis elegans has unique properties making it particularly advantageous for studies of the nervous system. The nervous system is composed of a stereotyped complement of neurons connected in a consistent manner. Here, we describe methods for studying nervous system structure and function. The transparency of the animal makes it possible to visualize and identify neurons in living animals with fluorescent probes. These methods have been recently enhanced for the efficient use of neuron-specific reporter genes. Because of its simple structure, for a number of years, C. elegans has been at the forefront of connectomic studies defining synaptic connectivity by electron microscopy. This field is burgeoning with new, more powerful techniques, and recommended up-to-date methods are here described that encourage the possibility of new work in C. elegans. Fluorescent probes for single synapses and synaptic connections have allowed verification of the EM reconstructions and for experimental approaches to synapse formation. Advances in microscopy and in fluorescent reporters sensitive to Ca2+ levels have opened the way to observing activity within single neurons across the entire nervous system.

scholarly journals Polycystin-2 ciliary extracellular vesicle release and targeting

2020 ◽  
Author(s):  
Juan Wang ◽  
Inna A. Nikonorova ◽  
Amanda Gu ◽  
Paul W. Sternberg ◽  
Maureen M. Barr
Keyword(s):  
Cell Communication ◽  
Extracellular Vesicle ◽  
Physiological Mechanisms ◽  
C Elegans ◽  
Evolutionarily Conserved ◽  
Sensory Capacity ◽  
Autosomal Dominant Polycystic Kidney ◽  
Sensory Evoked ◽  
And Function ◽  
Regenerative Therapies

Extracellular vesicles (EVs) are emerging as a universal means of cell-to-cell communication and hold great potential in diagnostics and regenerative therapies [1]. An urgent need in the field is a fundamental understanding of physiological mechanisms driving EV generation and function. Ciliary EVs act as signaling devices in Chlamydomonas and C. elegans [2–4]. Mammalian cilia shed EVs to eliminate unwanted receptors [5] or to retract cilia before entering the cell cycle [6]. Here we used our established C. elegans model to study sensory-evoked ciliary EV release and targeting using a fluorescently labeled EV cargo polycystin-2 (PKD-2). In C. elegans and mammals, the Autosomal Dominant Polycystic Kidney Disease (ADPKD) gene products polycystin-1 and polycystin-2 localize to cilia and EVs, act in the same genetic pathway, and function in a sensory capacity, suggesting ancient conservation [7]. We find that males deposit PKD-2-carrying EVs onto the vulva of the hermaphrodite during mating. We also show that mechanical stimulation triggers release of PKD-2-carrying EVs from cilia. To our knowledge this is the first report of mechanoresponsive nature of the ciliary EV release and of ciliary EV directional transfer from one animal to another animal. Since the polycystins are evolutionarily conserved ciliary EV cargoes, our findings suggest that similar mechanisms for EV release and targeting may occur in other systems and biological contexts.

Structural modifications of intercellular junctions.

1978 ◽  
Vol 36 (2) ◽  
pp. 330-331
Author(s):  
J. Metz ◽  
M. Merlo ◽  
W. G. Forssmann
Keyword(s):  
Gap Junctions ◽  
Intercellular Junctions ◽  
Cell Isolation ◽  
Extrahepatic Cholestasis ◽  
Structural Modifications ◽  
Pancreatic Duct Ligation ◽  
Pancreatic Cells ◽  
Duct Ligation ◽  
Thin Sectioning ◽  
And Function

Structure and function of intercellular junctions were studied under the electronmicroscope using conventional thin sectioning and freeze-etch replicas. Alterations of tight and gap junctions were analyzed 1. of exocrine pancreatic cells under cell isolation conditions and pancreatic duct ligation and 2. of hepatocytes during extrahepatic cholestasis.During the different steps of cell isolation of exocrine pancreatic cells, gradual changes of tight and gap junctions were observed. Tight junctions, which formed belt-like structures around the apex of control acinar cells in situ, subsequently diminished, became interrupted and were concentrated into macular areas (Fig. 1). Aggregations of membrane associated particles, which looked similar to gap junctions, were intermixed within tight junctional areas (Fig. 1). These structures continously disappeared in the last stages of the isolation procedure. The intercellular junctions were finally separated without destroying the integrity of the cell membrane, which was confirmed with porcion yellow, lanthanum chloride and horse radish peroxidase.

Structure of contact sites between the outer and inner mitochondrial membranes investigated by HVEM tomography

1996 ◽  
Vol 54 ◽  
pp. 966-967
Author(s):  
C.A. Mannella ◽  
K.F. Buttle ◽  
K.A. O‘Farrell ◽  
A. Leith ◽  
M. Marko
Keyword(s):  
Liver Mitochondrion ◽  
Adenine Nucleotide ◽  
Protein Complexes ◽  
Mitochondrial Membranes ◽  
Electron Microscopic ◽  
Contact Sites ◽  
Transmission Electron ◽  
Precursor Proteins ◽  
Membrane Contacts ◽  
And Function

Early transmission electron microscopy of plastic-embedded, thin-sectioned mitochondria indicated that there are numerous junctions between the outer and inner membranes of this organelle. More recent studies have suggested that the mitochondrial membrane contacts may be the site of protein complexes engaged in specialized functions, e.g., import of mitochondrial precursor proteins, adenine nucleotide channeling, and even intermembrane signalling. It has been suggested that the intermembrane contacts may be sites of membrane fusion involving non-bilayer lipid domains in the two membranes. However, despite growing interest in the nature and function of intramitochondrial contact sites, little is known about their structure.We are using electron microscopic tomography with the Albany HVEM to determine the internal organization of mitochondria. We have reconstructed a 0.6-μm section through an isolated, plasticembedded rat-liver mitochondrion by combining 123 projections collected by tilting (+/- 70°) around two perpendicular tilt axes. The resulting 3-D image has confirmed the basic inner-membrane organization inferred from lower-resolution reconstructions obtained from single-axis tomography.

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