Dendritic Actin Cytoskeleton: Structure, Functions, and Regulations (original) (raw)
Related papers
Periodic F-actin structures shape the neck of dendritic spines
Scientific Reports, 2016
Most of the excitatory synapses on principal neurons of the forebrain are located on specialized structures called dendritic spines. Their morphology, comprising a spine head connected to the dendritic branch via a thin neck, provides biochemical and electrical compartmentalization during signal transmission. Spine shape is defined and tightly controlled by the organization of the actin cytoskeleton. Alterations in synaptic strength correlate with changes in the morphological appearance of the spine head and neck. Therefore, it is important to get a better understanding of the nanoscale organization of the actin cytoskeleton in dendritic spines. A periodic organization of the actin/spectrin lattice was recently discovered in axons and a small fraction of dendrites using super-resolution microscopy. Here we use a small probe phalloidin-Atto647N, to label F-actin in mature hippocampal primary neurons and in living hippocampal slices. STED nanoscopy reveals that in contrast to β-II spe...
The Journal of Comparative Neurology, 2001
Dendritic spines differ considerably in their size, shape, and internal organization between brain regions. We examined the actin cytoskeleton in dendritic spines in hippocampus (areas CA1, CA3, and dentate gyrus), neostriatum, and cerebellum at both light and electron microscopic levels by using a novel high-resolution photoconversion method based in the high affinity of phalloidin for filamentous (F)-actin. In all brain regions, labeling was strongest in the heads of dendritic spines, diminishing in the spine neck. The number of labeled spines varied by region. Compared with the cerebellar molecular layer and area CA3, where nearly every dendritic spine was labeled, less than half the spines were labeled in CA1, dentate gyrus, and neostriatum. Serial section reconstructions of spines in these areas indicated that phalloidin labeling was restricted to the largest and most morphologically diverse dendritic spines. The resolution of the photoconversion technique allowed us to examine the localization and organization of actin filaments in the spine. The most intense staining for actin was found in the postsynaptic density and associated with the spines internal membrane system. In mushroom-shaped spines, F-actin staining was particularly strong between the lamellae of the spine apparatus. Three-dimensional reconstruction of labeled spines by using electron tomography showed that the labeled dense material was in continuity with the postsynaptic density. These results highlight differences in the actin cytoskeleton between different spine populations and provide novel information on the organization of the actin cytoskeleton in vivo.
Actin cytoskeleton in dendritic spine development and plasticity
Current Opinion in Neurobiology, 2016
Synapses are the basic unit of neuronal communication and their disruption is associated with many neurological disorders. Significant progress has been made towards understanding the molecular and genetic regulation of synapse formation, modulation, and dysfunction, but the underlying cellular mechanisms remain incomplete. The actin cytoskeleton not only provides the structural foundation for synapses, but also regulates a diverse array of cellular activities underlying synaptic function. Here we will discuss the regulation of the actin cytoskeleton in dendritic spines, the postsynaptic compartment of excitatory synapses. We will focus on a select number of actin regulatory processes, highlighting recent advances, the complexity of crosstalk between different pathways, and the challenges of understanding their precise impact on the structure and function of synapses.
The EMBO journal, 2014
Actin dynamics drive morphological remodeling of neuronal dendritic spines and changes in synaptic transmission. Yet, the spatiotemporal coordination of actin regulators in spines is unknown. Using single protein tracking and super-resolution imaging, we revealed the nanoscale organization and dynamics of branched F-actin regulators in spines. Branched F-actin nucleation occurs at the PSD vicinity, while elongation occurs at the tip of finger-like protrusions. This spatial segregation differs from lamellipodia where both branched F-actin nucleation and elongation occur at protrusion tips. The PSD is a persistent confinement zone for IRSp53 and the WAVE complex, an activator of the Arp2/3 complex. In contrast, filament elongators like VASP and formin-like protein-2 move outwards from the PSD with protrusion tips. Accordingly, Arp2/3 complexes associated with F-actin are immobile and surround the PSD. Arp2/3 and Rac1 GTPase converge to the PSD, respectively, by cytosolic and free-diff...
Actin Assemblies in the Axon Shaft – some Open Questions
Current Opinion in Neurobiology, 2018
The actin cytoskeleton in neurons plays critical roles in axonal growth and synaptic organization. Until recently, most studies on axonal actin were limited to terminal growth cones or synapses, whereas the organization of actin along the shaft of the axon was relatively ignored. However, experiments using super-resolution microscopy and live imaging have revealed previously unknown actin structures along the axonal shaft, such as periodic 'actin rings' circumferentially wrapping underneath the plasma membrane and dynamic actin pools deeper within the axon shaft (termed actin 'hotspots' and 'trails'). In this short review, we highlight some open questions that have surfaced as a direct result of these discoveries.
Regulation of Actin Filaments During Neurite Extension and Guidance
Advances in Neurobiology, 2010
Behavior and other neural functions are based on neural circuits that develop over a prolonged period, which lasts in humans from the second fetal month through postnatal years. These circuits develop as neurons extend complex cytoplasmic processes, long axons and highly branched dendrites, expressing intrinsic morphogenetic behaviors while interacting with other cells and molecules of the developing organism. Actin-based motility dominates this morphogenetic process of developing neural circuits. Actin, always one of the most abundant intracellular proteins in neurons, is expressed at its highest levels during neuronal morphogenesis ). An analysis of the actin content of embryonic sympathetic neurons indicated that actin comprises up to 20% of total cell protein (Fine and Bray 1971). Much of this actin is used in the motility that drives the formation of axons and dendrites. This chapter describes the roles of actin in the intrinsic mechanisms of morphogenesis of axons and dendrites and the extrinsic environmental features that regulate where and when axons and dendrites grow.
Accelerators, Brakes, and Gears of Actin Dynamics in Dendritic Spines
The Open Neuroscience Journal, 2009
Dendritic spines are actin-rich structures that accommodate the postsynaptic sites of most excitatory synapses in the brain. Although dendritic spines form and mature as synaptic connections develop, they remain plastic even in the adult brain, where they can rapidly grow, change, or collapse in response to normal physiological changes in synaptic activity that underlie learning and memory. Pathological stimuli can adversely affect dendritic spine shape and number, and this is seen in neurodegenerative disorders and some forms of mental retardation and autism as well. Many of the molecular signals that control these changes in dendritic spines act through the regulation of filamentous actin (F-actin), some through direct interaction with actin, and others via downstream effectors. For example, cortactin, cofilin, and gelsolin are actin-binding proteins that directly regulate actin dynamics in dendritic spines. Activities of these proteins are precisely regulated by intracellular signaling events that control their phosphorylation state and localization. In this review, we discuss how actin-regulating proteins maintain the balance between F-actin assembly and disassembly that is needed to stabilize mature dendritic spines, and how changes in their activities may lead to rapid remodeling of dendritic spines.
The Yin–Yang of Dendrite Morphology: Unity of Actin and Microtubules
Molecular Neurobiology, 2008
Actin and microtubules (MT) are targets of numerous molecular pathways that control neurite outgrowth. To generate a neuronal protrusion, coordinated structural changes of the actin and MT cytoskeletons must occur. Neurite formation occurs when actin filaments (Factin) are destabilized, filopodia are extended, and MTs invade filopodia. This process results in either axon or dendrite formation. Axonal branching involves interplay between F-actin and MTs, with F-actin and MTs influencing polymerization, stabilization, and maintenance of each other. Our knowledge of the mechanisms regulating development of the axon, however, far eclipses our understanding of dendritic development and branching. The two classes of neurites, while fundamentally similar in their ability to elongate and branch, dramatically differ in growth rate, orientation of polarized MT bundles, and mechanisms that initiate branching. In this review, we focus on how F-actin, MTs, and proteins that link the two cytoskeletons coordinate to specifically initiate dendritic events. Fig. 1 Basic differences in axonal and dendritic structures. a Dendrites are characterized by rough surfaces, widely spaced microtubules, and the presence of MAP2 protein. Microtubule − and +ends are not aligned. PSD proteins are localized at actin-rich dendritic spines. b Axons are characterized by tightly packed microtubules and the presence of tau protein. Microtubules are aligned at − and +ends Mol Neurobiol (2008) 38:270-284 271 271
Actomyosin Dynamics Determine the Extension and Retraction of Filopodia on Neuronal Dendrites
2016
Impact StatementIn this study, using a combination of computational and experimental approaches we show that a complex dynamic behavior of dendritic filopodia that is essential for synaptogenesis is explained by an interplay among forces generated by actin retrograde flow, myosin contractility, and substrate adhesion.Dendritic filopodia are actin-filled dynamic subcellular structures that sprout on neuronal dendrites during neurogenesis. The exploratory motion of the filopodia is crucial for synaptogenesis but the underlying mechanisms are poorly understood. To study the filopodial motility, we collected and analyzed image data on filopodia in cultured rat hippocampal neurons. We hypothesized that mechanical feedback among the actin retrograde flow, myosin activity and substrate adhesion gives rise to various filopodial behaviors. We have formulated a minimal one-dimensional partial differential equation model that reproduced the range of observed motility. To validate our model, we...