scholarly journals Cargo crowding at actin-rich regions along axons causes local traffic jams in neurons

2017 ◽  
Author(s):  
Parul Sood ◽  
Kausalya Murthy ◽  
T. Vinod Kumar ◽  
Michael L Nonet ◽  
Gautam I. Menon ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
General Feature ◽  
Substantial Fraction ◽  
Broad Distribution ◽  
Neuronal Process ◽  
Sources And Sinks ◽  
C Elegans ◽  
Traffic Jams ◽  
Touch Receptor Neurons ◽  
Receptor Neurons

ABSTRACTSteady axonal cargo flow is central to the functioning of healthy neurons. However, a substantial fraction of cargo in axons remains stationary across a broad distribution of times. We examine the transport of pre-synaptic vesicles (pre-SVs), endosomes and mitochondria in C. elegans touch receptor neurons (TRNs), showing that stalled cargo are predominantly present at actin-rich regions along the neuronal process. Cargo stalled at actin-rich regions increase the propensity of moving cargo to stall at the same location, resulting in traffic jams. Such local traffic jams at actin-rich regions are likely to be a general feature of axonal transport since they occur in Drosophila neurons as well. These traffic jams can act as both sources and sinks of vesicles. We propose that they act as functional reservoirs that contribute to maintaining robust cargo flow in the neuron.

scholarly journals Regulated distribution of mitochondria in touch receptor neurons of C. elegans influences touch response

2020 ◽  
Author(s):  
Anjali Awasthi ◽  
Souvik Modi ◽  
Sneha Hegde ◽  
Anusheela Chatterjee ◽  
Sudip Mondal ◽  
...  
Keyword(s):  
Molecular Motors ◽  
Neuronal Function ◽  
Mitochondrial Density ◽  
Neuronal Process ◽  
C Elegans ◽  
Touch Receptor Neurons ◽  
Touch Response ◽  
Receptor Neurons ◽  
Touch Receptor Neuron

AbstractDensity of mitochondria and their localization at specific sub-cellular regions of the neurons is regulated by molecular motors, their adaptors and the cytoskeleton. However, the regulation of the mitochondrial density, the positioning of mitochondria along the neuronal process and the role of axonal mitochondria in neuronal function remain poorly understood. This study shows that the density of mitochondria in C. elegans touch receptor neuron processes remains constant through development. Simulations show that mitochondrial positioning along parts of the neuronal process that are devoid of synapses is regulated. Additionally, we also demonstrate that axonal mitochondria are necessary for maintaining touch responsiveness.

scholarly journals Tracking mitochondrial density and positioning along a growing neuronal process in individual C. elegans neuron using a long-term growth and imaging microfluidic device

2020 ◽  
Author(s):  
Sudip Mondal ◽  
Jyoti Dubey ◽  
Anjali Awasthi ◽  
Guruprasad Reddy Sure ◽  
Sandhya P. Koushika
Keyword(s):  
Microfluidic Device ◽  
Neuronal Process ◽  
C Elegans ◽  
Cellular Events ◽  
Touch Receptor Neurons ◽  
Intracellular Organelles ◽  
Resolution Imaging ◽  
Receptor Neurons

AbstractThe long cellular architecture of neurons requires regulation in part through transport and anchoring events to distribute intracellular organelles. During development, cellular and sub-cellular events such as organelle additions and their recruitment at specific sites on the growing axons occur over different time scales and often show inter-animal variability thus making it difficult to identify specific phenomena in population averages. To measure the variability in sub-cellular events such as organelle positions, we developed a microfluidic device to feed and immobilize C. elegans for high-resolution imaging over several days. The microfluidic device enabled long-term imaging of individual animals and allowed us to investigate organelle density using mitochondria as a testbed in a growing neuronal process in vivo. Sub-cellular imaging of an individual neuron in multiple animals, over 36 hours in our microfluidic device, shows the addition of new mitochondria along the neuronal process and an increase in the accumulation of synaptic vesicles at synapses, both organelles with important roles in neurons. Long-term imaging of individual C. elegans touch receptor neurons identifies addition of new mitochondria and interacts with other moving mitochondria only through fission and fusion events. The addition of new mitochondria takes place along the entire neuronal process length and the threshold for the addition of a new mitochondrion is when the average separation between the two pre-existing mitochondria exceeds 24 micrometers.

scholarly journals Touch-induced Mechanical Strain in Somatosensory Neurons is Independent of Extracellular Matrix Mutations in C. elegans

2019 ◽  
Author(s):  
Adam L. Nekimken ◽  
Beth L. Pruitt ◽  
Miriam B. Goodman
Keyword(s):  
Extracellular Matrix ◽  
Fluorescent Protein ◽  
Mechanical Strain ◽  
C Elegans ◽  
Mechanosensory Neurons ◽  
State Touch ◽  
Touch Receptor Neurons ◽  
Somatosensory Neurons ◽  
Measured Strain ◽  
Receptor Neurons

AbstractCutaneous mechanosensory neurons are activated by mechanical loads applied to the skin, and these stimuli are proposed to generate mechanical strain within sensory neurons. Using a microfluidic device to deliver controlled stimuli to intact animals and large, immobile, and fluorescent protein-tagged mitochondria as fiducial markers in the touch receptor neurons (TRNs), we visualized and measured touch-induced mechanical strain in C. elegans worms. At steady-state, touch stimuli sufficient to activate TRNs induce an average strain of 3.1% at the center of the actuator and this strain decays to near zero at the edges of the actuator. We also measured strain in animals carrying mutations affecting links between the extracellular matrix (ECM) and the TRNs but could not detect any differences in touch-induced mechanical strain between wild-type and mutant animals. Collectively, these results demonstrate that touching the skin induces local mechanical strain in intact animals and suggest that a fully intact ECM is not essential for transmitting mechanical strain from the skin to cutaneous mechanosensory neurons.

scholarly journals MEC-2 Is Recruited to the Putative Mechanosensory Complex in C. elegans Touch Receptor Neurons through Its Stomatin-like Domain

2004 ◽  
Vol 14 (21) ◽  
pp. 1888-1896 ◽  
Author(s):  
Shifang Zhang ◽  
Johanna Arnadottir ◽  
Charles Keller ◽  
Guy A. Caldwell ◽  
C.Andrea Yao ◽  
...  
Keyword(s):  
C Elegans ◽  
Touch Receptor Neurons ◽  
Receptor Neurons

scholarly journals Comparing Caenorhabditis elegans gentle and harsh touch response behavior using a multiplexed hydraulic microfluidic device

2017 ◽  
Author(s):  
Patrick D. McClanahan ◽  
Joyce H. Xu ◽  
Christopher Fang-Yen
Keyword(s):  
Caenorhabditis Elegans ◽  
Microfluidic Device ◽  
Receptive Fields ◽  
The Body ◽  
Mechanical Stimuli ◽  
C Elegans ◽  
Response Characteristics ◽  
Touch Receptor Neurons ◽  
Touch Response ◽  
Receptor Neurons

AbstractThe roundworm Caenorhabditis elegans is an important model system for understanding the genetics and physiology of touch. Classical assays for C. elegans touch, which involve manually touching the animal with a probe and observing its response, are limited by their low throughput and qualitative nature. We developed a microfluidic device in which several dozen animals are subject to spatially localized mechanical stimuli with variable amplitude. The device contains 64 sinusoidal channels through which worms crawl, and hydraulic valves that deliver touch stimuli to the worms. We used this assay to characterize the behavioral responses to gentle touch stimuli and the less well studied harsh (nociceptive) touch stimuli. First, we measured the relative response thresholds of gentle and harsh touch. Next, we quantified differences in the receptive fields between wild type worms and a mutant with non-functioning posterior touch receptor neurons. We showed that under gentle touch the receptive field of the anterior touch receptor neurons extends into the posterior half of the body. Finally, we found that the behavioral response to gentle touch does not depend on the locomotion of the animal immediately prior to the stimulus, but does depend on the location of the previous touch. Responses to harsh touch, on the other hand, did not depend on either previous velocity or stimulus location. Differences in gentle and harsh touch response characteristics may reflect the different innervation of the respective mechanosensory cells. Our assay will facilitate studies of mechanosensation, sensory adaptation, and nociception.

scholarly journals Epistatic, Synthetic, and Balancing Interactions among Tubulin Missense Mutations Affecting Neurite Growth in Caenorhabditis elegans

2020 ◽  
pp. mbc.E20-07-0492
Author(s):  
Ho Ming Terence Lee ◽  
Natalie Yvonne Sayegh ◽  
A. Sophia Gayek ◽  
Susan Laura Javier Jao ◽  
Martin Chalfie ◽  
...  
Keyword(s):  
Genetic Interaction ◽  
Neurite Growth ◽  
Phenotypic Characterization ◽  
Missense Mutations ◽  
Loss Of Function ◽  
C Elegans ◽  
Touch Receptor Neurons ◽  
Receptor Neurons ◽  
Tubulin Mutations

Mutations in tubulins affect microtubule (MT) dynamics and functions during neuronal differentiation and their genetic interaction provides insights into the regulation of MT functions. We previously used C. elegans touch receptor neurons to analyze the cellular impact of tubulin mutations and reported the phenotypes of 67 tubulin missense mutations, categorized into three classes: loss-of-function ( lf), antimorphic ( anti), and neomorphic ( neo) alleles. In this study, we isolated 54 additional tubulin alleles through suppressor screens in sensitized backgrounds that caused excessive neurite growth. These alleles included 32 missense mutations not analyzed before, bringing the total number of mutations in our collection to 99. Phenotypic characterization of these newly isolated mutations identified three new types of alleles: partial lf and weak neo alleles of mec-7/β-tubulin that had subtle effects and strong anti alleles of mec-12/α-tubulin. We also discovered complex genetic interactions among the tubulin mutations, including the suppression of neo mutations by intragenic lf and anti alleles, additive and synthetic effects between mec-7 neo alleles, and unexpected epistasis, in which weaker neo alleles masked the effects of stronger neo alleles in inducing ectopic neurite growth. We also observed balancing between neo and anti alleles, whose respective MT-hyperstablizing and -destabilizing effects neutralized each other.

scholarly journals Extracellular Proteins Organize the Mechanosensory Channel Complex in C. elegans Touch Receptor Neurons

Neuron ◽  
2004 ◽  
Vol 44 (5) ◽  
pp. 795-807 ◽  
Author(s):  
Lesley Emtage ◽  
Guoqiang Gu ◽  
Erika Hartwieg ◽  
Martin Chalfie
Keyword(s):  
Extracellular Proteins ◽  
C Elegans ◽  
Touch Receptor Neurons ◽  
Receptor Neurons

scholarly journals Structural and functional diversity in the neuronal microtubules of Caenorhabditis elegans.

1982 ◽  
Vol 93 (1) ◽  
pp. 15-23 ◽  
Author(s):  
M Chalfie ◽  
J N Thomson
Keyword(s):  
Caenorhabditis Elegans ◽  
Colchicine Treatment ◽  
Variable Number ◽  
Sensory Transduction ◽  
Partial Replacement ◽  
C Elegans ◽  
Touch Receptor Neurons ◽  
Touch Sensitivity ◽  
Receptor Neurons

Tannic acid fixation reveals differences in the number of protofilaments between microtubules (MTs) in the nematode Caenorhabditis elegans. Most cells have MTs with 11 protofilaments but the six touch receptor neurons (the microtubule cells) have MTs with 15 protofilaments. No 13-protofilament (13-p) MT has been seen. The modified cilia of sensory neurons also possess unusual structures. The cilia contain nine outer doublets with A subfibers of 13 protofilaments and B subfibers of 11 protofilaments and a variable number of inner singlet MTs containing 11 protofilaments. The 15-p MTs but not the 11-p MTs are eliminated by colchicine-treatment or by mutation of the gene mec-7. Concomitantly, touch sensitivity is also lost. However, whereas colchicine treatment leads to the loss of all MTs from the microtubule cells, mutations in mec-7 result in the partial replacement of the 15-p MTs with 11-p MTs. Benzimidazoles (benomyl and nocodazole) have more general effects on C. elegans (slow growth, severe uncoordination, and loss of processes from the ventral cord) but do not affect the 15-p MTs. Benomyl will, however, disrupt the replacement 11-p MTs found in the microtubule cells of mec-7 mutants. The 11-p and 15-p MTs also respond differently to temperature and fixation conditions. It is likely that either type of MT will suffice for the proper outgrowth of the microtubule cell process, but only the 15-p MT can function in the specialized role of sensory transduction of the microtubule cells.

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