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

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

Cells ◽

10.3390/cells9092006 ◽

2020 ◽

Vol 9 (9) ◽

pp. 2006

Author(s):

Marina Mikhaylova ◽

Jakob Rentsch ◽

Helge Ewers

Keyword(s):

Structural Properties ◽

Growth Cone ◽

Dendritic Spines ◽

Initial Segment ◽

Research Topics ◽

Actomyosin Contractility ◽

Axonal Diameter ◽

And Function ◽

Muscle Myosin ◽

Actomyosin Contraction

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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T-BET and EOMES Accelerate and Enhance Functional Differentiation of Human Natural Killer Cells

Frontiers in Immunology ◽

10.3389/fimmu.2021.732511 ◽

2021 ◽

Vol 12 ◽

Author(s):

Laura Kiekens ◽

Wouter Van Loocke ◽

Sylvie Taveirne ◽

Sigrid Wahlen ◽

Eva Persyn ◽

...

Keyword(s):

Nk Cells ◽

Natural Killer ◽

Cell Biology ◽

Nk Cell ◽

Current Knowledge ◽

Functional Differentiation ◽

Cell Maturation ◽

Hematopoietic Stem ◽

And Function

T-bet and Eomes are transcription factors that are known to be important in maturation and function of murine natural killer (NK) cells. Reduced T-BET and EOMES expression results in dysfunctional NK cells and failure to control tumor growth. In contrast to mice, the current knowledge on the role of T-BET and EOMES in human NK cells is rudimentary. Here, we ectopically expressed either T-BET or EOMES in human hematopoietic progenitor cells. Combined transcriptome, chromatin accessibility and protein expression analyses revealed that T-BET or EOMES epigenetically represses hematopoietic stem cell quiescence and non-NK lineage differentiation genes, while activating an NK cell-specific transcriptome and thereby drastically accelerating NK cell differentiation. In this model, the effects of T-BET and EOMES are largely overlapping, yet EOMES shows a superior role in early NK cell maturation and induces faster NK receptor and enhanced CD16 expression. T-BET particularly controls transcription of terminal maturation markers and epigenetically controls strong induction of KIR expression. Finally, NK cells generated upon T-BET or EOMES overexpression display improved functionality, including increased IFN-γ production and killing, and especially EOMES overexpression NK cells have enhanced antibody-dependent cellular cytotoxicity. Our findings reveal novel insights on the regulatory role of T-BET and EOMES in human NK cell maturation and function, which is essential to further understand human NK cell biology and to optimize adoptive NK cell therapies.

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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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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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Vascular Endothelial Cell Biology: An Update

International Journal of Molecular Sciences ◽

10.3390/ijms20184411 ◽

2019 ◽

Vol 20 (18) ◽

pp. 4411 ◽

Cited By ~ 75

Author(s):

Krüger-Genge ◽

Blocki ◽

Franke ◽

Jung

Keyword(s):

Endothelial Cells ◽

Cell Biology ◽

Current Knowledge ◽

Regional Blood Flow ◽

Vascular Endothelial Cell ◽

Inflammatory Cells ◽

The Body ◽

Arterial Tree ◽

Foreign Materials ◽

And Function

The vascular endothelium, a monolayer of endothelial cells (EC), constitutes the inner cellular lining of arteries, veins and capillaries and therefore is in direct contact with the components and cells of blood. The endothelium is not only a mere barrier between blood and tissues but also an endocrine organ. It actively controls the degree of vascular relaxation and constriction, and the extravasation of solutes, fluid, macromolecules and hormones, as well as that of platelets and blood cells. Through control of vascular tone, EC regulate the regional blood flow. They also direct inflammatory cells to foreign materials, areas in need of repair or defense against infections. In addition, EC are important in controlling blood fluidity, platelet adhesion and aggregation, leukocyte activation, adhesion, and transmigration. They also tightly keep the balance between coagulation and fibrinolysis and play a major role in the regulation of immune responses, inflammation and angiogenesis. To fulfill these different tasks, EC are heterogeneous and perform distinctly in the various organs and along the vascular tree. Important morphological, physiological and phenotypic differences between EC in the different parts of the arterial tree as well as between arteries and veins optimally support their specified functions in these vascular areas. This review updates the current knowledge about the morphology and function of endothelial cells, particularly their differences in different localizations around the body paying attention specifically to their different responses to physical, biochemical and environmental stimuli considering the different origins of the EC.

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A Perspective on the Role of Dynamic Alternative RNA Splicing in the Development, Specification, and Function of Axon Initial Segment

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2019.00295 ◽

2019 ◽

Vol 12 ◽

Cited By ~ 2

Author(s):

Takatoshi Iijima ◽

Takeshi Yoshimura

Keyword(s):

Rna Splicing ◽

Initial Segment ◽

Axon Initial Segment ◽

And Function

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The Ringleaders: Understanding the Apicomplexan Basal Complex Through Comparison to Established Contractile Ring Systems

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.656976 ◽

2021 ◽

Vol 11 ◽

Author(s):

Alexander A. Morano ◽

Jeffrey D. Dvorin

Keyword(s):

Cell Biology ◽

Myosin Ii ◽

Ring Structure ◽

Plastid Division ◽

Contractile Ring ◽

Ring Systems ◽

Basal Complex ◽

And Function

The actomyosin contractile ring is a key feature of eukaryotic cytokinesis, conserved across many eukaryotic kingdoms. Recent research into the cell biology of the divergent eukaryotic clade Apicomplexa has revealed a contractile ring structure required for asexual division in the medically relevant genera Toxoplasma and Plasmodium; however, the structure of the contractile ring, known as the basal complex in these parasites, remains poorly characterized and in the absence of a myosin II homolog, it is unclear how the force required of a cytokinetic contractile ring is generated. Here, we review the literature on the basal complex in Apicomplexans, summarizing what is known about its formation and function, and attempt to provide possible answers to this question and suggest new avenues of study by comparing the Apicomplexan basal complex to well-studied, established cytokinetic contractile rings and their mechanisms in organisms such as S. cerevisiae and D. melanogaster. We also compare the basal complex to structures formed during mitochondrial and plastid division and cytokinetic mechanisms of organisms beyond the Opisthokonts, considering Apicomplexan diversity and divergence.

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