Actomyosin Contractility in the Generation and Plasticity of Axons and Dendritic Spines

Actin and non-muscle myosins have long been known to play important roles in growth cone steering and neurite outgrowth. More recently, novel functions for non-muscle myosin have been described in axons and dendritic spines. Consequently, possible roles of actomyosin contraction in organizing and maintaining structural properties of dendritic spines, the size and location of axon initial segment and axonal diameter are emerging research topics. In this review, we aim to summarize recent findings involving myosin localization and function in these compartments and to discuss possible roles for actomyosin in their function and the signaling pathways that control them.

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Non-Muscle Myosin II in Axonal Cell Biology: From the Growth Cone to the Axon Initial Segment

Cells ◽

10.3390/cells9091961 ◽

2020 ◽

Vol 9 (9) ◽

pp. 1961

Author(s):

Ana Rita Costa ◽

Monica M. Sousa

Keyword(s):

Spatial Distribution ◽

Growth Cone ◽

Cell Biology ◽

Initial Segment ◽

Current Knowledge ◽

Myosin Ii ◽

Axon Growth ◽

Axon Initial Segment ◽

And Function ◽

Muscle Myosin

By binding to actin filaments, non-muscle myosin II (NMII) generates actomyosin networks that hold unique contractile properties. Their dynamic nature is essential for neuronal biology including the establishment of polarity, growth cone formation and motility, axon growth during development (and axon regeneration in the adult), radial and longitudinal axonal tension, and synapse formation and function. In this review, we discuss the current knowledge on the spatial distribution and function of the actomyosin cytoskeleton in different axonal compartments. We highlight some of the apparent contradictions and open questions in the field, including the role of NMII in the regulation of axon growth and regeneration, the possibility that NMII structural arrangement along the axon shaft may control both radial and longitudinal contractility, and the mechanism and functional purpose underlying NMII enrichment in the axon initial segment. With the advances in live cell imaging and super resolution microscopy, it is expected that in the near future the spatial distribution of NMII in the axon, and the mechanisms by which it participates in axonal biology will be further untangled.

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Homeostatic plasticity rules control the wiring of axo-axonic synapses at the axon initial segment

10.1101/453753 ◽

2018 ◽

Cited By ~ 1

Author(s):

Alejandro Pan-Vazquez ◽

Winnie Wefelmeyer ◽

Victoria Gonzalez Sabater ◽

Juan Burrone

Keyword(s):

Initial Segment ◽

Pyramidal Cells ◽

Axon Initial Segment ◽

Homeostatic Plasticity ◽

Network Activity ◽

Gabaergic Interneuron ◽

Chandelier Cells ◽

Local Circuits ◽

And Function

AbstractGABAergic interneurons are chiefly responsible for controlling the activity of local circuits in the cortex1,2. However, the rules that govern the wiring of interneurons are not well understood3. Chandelier cells (ChCs) are a type of GABAergic interneuron that control the output of hundreds of neighbouring pyramidal cells through axo-axonic synapses which target the axon initial segment (AIS)4. Despite their importance in modulating circuit activity, our knowledge of the development and function of axo-axonic synapses remains elusive. In this study, we investigated the role of activity in the formation and plasticity of ChC synapses. In vivo imaging of ChCs during development uncovered a narrow window (P12-P18) over which axons arborized and formed connections. We found that increases in the activity of either pyramidal cells or individual ChCs during this temporal window resulted in a reversible decrease in axo-axonic connections. Voltage imaging of GABAergic transmission at the AIS showed that axo-axonic synapses were depolarising during this period. Identical manipulations of network activity in older mice (P40-P46), when ChC synapses are inhibitory, resulted in an increase in axo-axonic synapses. We propose that the direction of ChC plasticity follows homeostatic rules that depend on the polarity of axo-axonic synapses.

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Non-muscle myosin-2 contractility-dependent actin turnover limits the length of epithelial microvilli

10.1101/2020.05.01.072389 ◽

2020 ◽

Cited By ~ 2

Author(s):

Colbie R. Chinowsky ◽

Julia A. Pinette ◽

Leslie M. Meenderink ◽

Matthew J. Tyska

Keyword(s):

Brush Border ◽

Isotropic Layer ◽

Intestinal Epithelial ◽

Actin Bundles ◽

Terminal Web ◽

Actin Turnover ◽

Genetic Perturbations ◽

And Function ◽

Pointed End ◽

Muscle Myosin

ABSTRACTEpithelial brush borders are large arrays of microvilli that enable efficient solute uptake from luminal spaces. In the context of the intestinal tract, brush border microvilli drive functions that are critical for physiological homeostasis, including nutrient uptake and host defense. However, cytoskeletal mechanisms that regulate the assembly and morphology of these protrusions are poorly understood. The parallel actin bundles that support microvilli have their pointed-end rootlets anchored in a highly crosslinked filamentous meshwork referred to as the “terminal web”. Although classic EM studies revealed complex ultrastructure, the composition, organization, and function of the terminal web remains unclear. Here, we identify non-muscle myosin-2C (NM2C) as a major component of the brush border terminal web. NM2C is found in a dense, isotropic layer of puncta across the sub-apical domain, which transects the rootlets of microvillar actin bundles. Puncta in this network are separated by ∼210 nm, dimensions that are comparable to the expected size of filaments formed by NM2C. In primary intestinal organoid cultures, the terminal web NM2C network is highly dynamic and exhibits continuous remodeling. Using pharmacological and genetic perturbations to disrupt NM2C activity in cultured intestinal epithelial cells, we found that this motor controls the length of growing microvilli by regulating actin turnover in a manner that requires a fully active motor domain. Our findings answer a decades old question on the function of terminal web myosin and hold broad implications for understanding apical morphogenesis in diverse epithelial systems.

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Tropomyosin Tpm3.1 is required to maintain the structure and function of the axon initial segment

10.1101/711614 ◽

2019 ◽

Cited By ~ 1

Author(s):

Amr Abouelezz ◽

Holly Stefen ◽

Mikael Segerstråle ◽

David Micinski ◽

Rimante Minkeviciene ◽

...

Keyword(s):

Actin Filaments ◽

Hippocampal Neurons ◽

Initial Segment ◽

Actin Polymerization ◽

Firing Frequency ◽

Axon Initial Segment ◽

Action Potential Initiation ◽

Sodium Ion Channels ◽

And Function ◽

Filament Network

ABSTRACTThe axon initial segment (AIS) is the site of action potential initiation and serves as a vesicular filter and diffusion barrier that help maintain neuronal polarity. Recent studies have revealed details about a specialized structural complex in the AIS. While an intact actin cytoskeleton is required for AIS formation, pharmacological disruption of actin polymerization compromises the AIS vesicle filter but does not affect overall AIS structure. In this study, we found that the tropomyosin isoform Tpm3.1 decorates a population of relatively stable actin filaments in the AIS. Inhibiting Tpm3.1 in cultured hippocampal neurons led to the loss of AIS structure, the AIS vesicle filter, the clustering of sodium ion channels, and reduced firing frequency. We propose that Tpm3.1-decorated actin filaments form a stable actin filament network under the AIS membrane which provides a scaffold for membrane organization and AIS proteins.

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Electrical and Ca2+ signaling in dendritic spines of substantia nigra dopaminergic neurons

eLife ◽

10.7554/elife.13905 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 5

Author(s):

Travis A Hage ◽

Yujie Sun ◽

Zayd M Khaliq

Keyword(s):

Dendritic Spines ◽

Dopaminergic Neurons ◽

Fluorescence Recovery After Photobleaching ◽

Dopamine Neurons ◽

Fixed Tissue ◽

Spine Length ◽

Relative Contribution ◽

Midbrain Dopamine ◽

Shaft Synapses ◽

And Function

Little is known about the density and function of dendritic spines on midbrain dopamine neurons, or the relative contribution of spine and shaft synapses to excitability. Using Ca2+ imaging, glutamate uncaging, fluorescence recovery after photobleaching and transgenic mice expressing labeled PSD-95, we comparatively analyzed electrical and Ca2+ signaling in spines and shaft synapses of dopamine neurons. Dendritic spines were present on dopaminergic neurons at low densities in live and fixed tissue. Uncaging-evoked potential amplitudes correlated inversely with spine length but positively with the presence of PSD-95. Spine Ca2+ signals were less sensitive to hyperpolarization than shaft synapses, suggesting amplification of spine head voltages. Lastly, activating spines during pacemaking, we observed an unexpected enhancement of spine Ca2+ midway throughout the spike cycle, likely involving recruitment of NMDA receptors and voltage-gated conductances. These results demonstrate functionality of spines in dopamine neurons and reveal a novel modulation of spine Ca2+ signaling during pacemaking.

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A Study of Hydrophobically Modified Pullulan Nanoparticles with Different Hydrophobic Densities on the Effect of Anti-Colon Cancer Cell Efficiency

Journal of Biomedical Nanotechnology ◽

10.1166/jbn.2021.3173 ◽

2021 ◽

Vol 17 (10) ◽

pp. 1972-1983

Author(s):

Yi Zhang ◽

Qing Jiang ◽

Xinyi Liu ◽

Liping Peng ◽

Xinyi Tang ◽

...

Keyword(s):

Colon Cancer ◽

Structural Properties ◽

Feed Ratio ◽

Cell Efficiency ◽

H Nmr ◽

Hydrophobically Modified ◽

Transmission Electron ◽

A Cell ◽

And Function ◽

Hct116 Cells

To discuss the effect of hydrophobic groups of a polymer on the structural properties and function of polymer nanoparticles (NPs), we grafted chenodeoxycholic acid (CDCA) with pullulan (PU) to form hydrophobically modified PU (PUC). Three PUC polymers, namely, PUC-1, PUC-2, and PUC-3, with different degrees of substitution were designed by changing the feed ratio of CDCA and PU. 1H-NMR spectra showed that the PUC polymer was successfully synthesized, and the degrees of hydrophobic substitution for PUC-1, PUC-2, and PUC-3 were calculated to be 10.66%, 13.92%, and 16.94%, respectively. The PUC NPs were prepared by the dialysis method and were shown to be uniformly spherical by transmission electron microscopy (TEM). The average sizes were about (220±10) nm, (203±7) nm, and (163±6) nm under dynamic light scattering (DLS) for PUC-1 NPs, PUC-2 NPs, and PUC-3 NPs, respectively. Drug release experiments showed that the three PUC/DOX NPs exhibited good sustained release. At 48 h, the IC50 of doxorubicin in inhibiting colon cancer HCT116 cells was 0.0904 μg/mL. A cell study showed that PUC-3/DOX NPs had the highest uptake efficiency by HCT116 cells with the most cytotoxicity and inhibited the migration of HCT116 cells with the highest efficiency. The structural properties and function of polymer NPs were closely related to the hydrophobic groups in the polymer, and NPs with higher hydrophobicity showed a smaller size, higher drug capacity, and greater cell efficiency.

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Long-term Memory Upscales Volume of Postsynaptic Densities in the Process that Requires Autophosphorylation of αCaMKII

Cerebral Cortex ◽

10.1093/cercor/bhz261 ◽

2019 ◽

Vol 30 (4) ◽

pp. 2573-2585 ◽

Cited By ~ 1

Author(s):

Małgorzata Alicja Śliwińska ◽

Anna Cały ◽

Malgorzata Borczyk ◽

Magdalena Ziółkowska ◽

Edyta Skonieczna ◽

...

Keyword(s):

Dendritic Spines ◽

Smooth Endoplasmic Reticulum ◽

Structural Data ◽

Long Term Memory ◽

Brain Circuits ◽

Hippocampal Area ◽

And Function ◽

And Storage ◽

Old Mice

Abstract It is generally accepted that formation and storage of memory relies on alterations of the structure and function of brain circuits. However, the structural data, which show learning-induced and long-lasting remodeling of synapses, are still very sparse. Here, we reconstruct 1927 dendritic spines and their postsynaptic densities (PSDs), representing a postsynaptic part of the glutamatergic synapse, in the hippocampal area CA1 of the mice that underwent spatial training. We observe that in young adult (5 months), mice volume of PSDs, but not the volume of the spines, is increased 26 h after the training. The training-induced growth of PSDs is specific for the dendritic spines that lack smooth endoplasmic reticulum and spine apparatuses, and requires autophosphorylation of αCaMKII. Interestingly, aging alters training-induced ultrastructural remodeling of dendritic spines. In old mice, both the median volumes of dendritic spines and PSDs shift after training toward bigger values. Overall, our data support the hypothesis that formation of memory leaves long-lasting footprint on the ultrastructure of brain circuits; however, the form of circuit remodeling changes with age.

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