Actin blobs prefigure dendrite branching sites

Nithianandam, Vanitha; Chien, Ching‐Te

doi:10.1083/jcb.201711136

Cited by 51 publications

(78 citation statements)

References 82 publications

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“…GMA is a genetically encoded GFP-tagged actinbinding domain of moesin (Edwards et al, 1997) and its accumulation suggests a rapid remodelling or nucleation of actin at the site of branch formation. Additionally, GMA and LifeAct, an alternative F-actin marker, localize in dynamic puncta in Drosophila sensory class IV da (cIVda) neurons, at sites of new branch formation (Nithianandam and Chien, 2018). The Arp2/3 complex is a strong candidate for reshaping actin at the site of branch formation, as it promotes dendrite branching in cultured hippocampal neurons (Dharmalingam et al, 2009;Zhang et al, 2017) and is a major target of the small GTPase Rac1, a conserved key regulator of dendrite morphology (Govek et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo

et al. 2019

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The formation of neuronal dendrite branches is fundamental for the wiring and function of the nervous system. Indeed, dendrite branching enhances the coverage of the neuron's receptive field and modulates the initial processing of incoming stimuli. Complex dendrite patterns are achieved in vivo through a dynamic process of de novo branch formation, branch extension and retraction. The first step towards branch formation is the generation of a dynamic filopodium-like branchlet. The mechanisms underlying the initiation of dendrite branchlets are therefore crucial to the shaping of dendrites. Through in vivo time-lapse imaging of the subcellular localization of actin during the process of branching of Drosophila larva sensory neurons, combined with genetic analysis and electron tomography, we have identified the Actin-related protein (Arp) 2/3 complex as the major actin nucleator involved in the initiation of dendrite branchlet formation, under the control of the activator WAVE and of the small GTPase Rac1. Transient recruitment of an Arp2/3 component marks the site of branchlet initiation in vivo. These data position the activation of Arp2/3 as an early hub for the initiation of branchlet formation.

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Section: Introductionmentioning

confidence: 99%

Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo

et al. 2019

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“…All neurons were imaged during the 3 rd instar larva stage, when the da neurons acquire their mature shapes. Cytoskeletal organization in control or mutant genetic backgrounds was assessed by using Class I-or Class IV-specific GAL4 to label respectively stable microtubules via the mCherry-tagged microtubule associated protein Jupiter (Cabernard and Doe, 2009;Das et al, 2017a;Weiner et al, 2016) (Figure 1 A, E, I, Figure S1 A, E, I, Figure S2) and F-actin by a GFPtagged Moesin actin binding domain (Figure 1 C, G, K, Figure S1 C, G, K) which has been previously validated and extensively utilized as a marker of F-actin (Anderson et al, 2005;Das et al, 2017a;Dutta et al, 2002;Jinushi-Nakao et al, 2007;Lee et al, 2011;Nagel et al, 2012;Nithianandam and Chien, 2018). Basic morphological reconstructions of these images consisted of vectorized tree structures composed of numerous, uniformly sampled, connected compartments.…”

Section: Resultsmentioning

confidence: 99%

“…Enrichment of F-actin near dendritic bifurcations also constitutes an arbor-wide validation of recent experimental observations. Actin blobs have been shown to stabilize at branch points, and nullifying that stabilization leads to a reduction in branch complexity (Nithianandam and Chien, 2018). Moreover, Arp2/3 complex temporarily localizes at dendritic bifurcations to nucleate actin, leading to actin remodeling at the nascent branch point (Sturner et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Recent in vivo studies have reported transient F-actin enrichment at da neuron branch points. One study demonstrated moving actin blobs that stabilize at branch points (Nithianandam and Chien, 2018). Another study showed that the Arp2/3 complex driven nucleation of actin initiates branch formation from the F-act enriched location (Sturner et al, 2019).…”

Section: Bifurcations Are Strongly Associated With Local F-actin Enrimentioning

confidence: 99%

“…While actin polymerization has been shown to drive neurite outgrowth (Chia et al, 2016), contrasting experiments have indicated that actin waves at growth cones do not initiate elongation and neurite outgrowth can occur without F-actin at neurite tips (Mortal et al, 2017). Possibly stabilizing actin blobs are also found at branch points (Nithianandam and Chien, 2018) and nucleation events have been involved in this punctate expression of F-actin (Sturner et al, 2019). Since the local densities of microtubules and F-actin have never been quantified arbor-wide in large numbers of neurons, the multifarious relation between arbor architecture and cytoskeletal composition remains incompletely understood.…”

Section: Introductionmentioning

confidence: 99%

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Distinct relations of microtubules and actin filaments with dendritic architecture

Nanda

Bhattacharjee

Cox

et al. 2019

Preprint

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Neuronal morphology underlies circuit connectivity and signal integration, thus profoundly affecting nervous system function. Although microtubules and F-actin have long been recognized as key determinants of dendritic morphology, their precise and distinct roles are yet to be fully elucidated. The lack of arbor-wide cytoskeletal information registered with neuromorphological measurements has so far limited direct observations of the interrelations between microtubules, F-actin and arbor architecture. Here we pair live confocal imaging of fluorescently labeled dendritic arborization (da) neurons in the fruit fly larva with our recently developed multi-signal neural tracing technique. We discovered that dendritic arbor length is highly dependent on local microtubule quantity, whereas local F-actin enrichment is associated with dendritic branching. Earlier computer simulations used quantifiable morphological features both as model parameters (e.g. branch thickness) and emergent properties (e.g. tree asymmetry). Multi-signal reconstructions allowed us to computationally simulate arbor structure solely constrained by experimentally measured, local subcellular distributions of microtubules and F-actin. The generative model yielded synthetic trees with morphological and molecular patterns statistically indistinguishable from those of real da neurons, demonstrating that these two investigated cytoskeletal components are sufficient to define dendritic architecture. The analysis and modeling outcomes hold true for the simplest (Class I) and the most complex (Class IV) da neuron subclasses. Moreover, local increases in the quantity of stable microtubules in Class IV neurons via Formin3 overexpression further strengthens the correlation between local microtubule quantity and dendritic arbor length as predicted by the model and reproduced in simulations. SUPPORT: NIH R01 NS39600 and NS086082 and BICCN U01 MH114829. SignificanceMicrotubules and F-actin are fundamental molecular factors in neuronal arbor architectural development. However, the elucidation of their exact roles in defining dendritic architecture has been hindered by the lack of arbor-wide cytoskeletal information in existing morphological data. Our recently developed enhanced digital tracing methodology allows the systematic quantification of subcellular protein distributions with overall morphology. These multi-signal reconstructions and the novel analyses reported in this study demonstrate two striking double-dissociations in cytoskeletal behavior: local microtubule is the best predictor of arbor length, while local enrichment in F-actin is strongly associated with branching. A computational model of arbor generation purely driven by local microtubule and F-actin quantities fully reproduces tree topology and dendritic cytoskeletal distributions. Moreover, these findings are robust across cell types and genetic alteration.

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Potential COVID‐19 therapeutic approaches targeting angiotensin‐converting enzyme 2; An updated review

Zanganeh

Goodarzi

Doroudian

et al. 2021

Reviews in Medical Virology

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COVID-19 has spread swiftly throughout the world posing a global health emergency. The significant numbers of deaths attributed to this pandemic have researchers battling to understand this new, dangerous virus. Researchers are looking to find possible treatment regimens and develop effective therapies. This study aims to provide an overview of published scientific information on potential treatments, emphasizing angiotensin-converting enzyme II (ACE2) inhibitors as one of the most important drug targets. SARS-CoV-2 receptor-binding domain (RBD); as a viral attachment or entry inhibitor against SARS-CoV-2, human recombinant soluble ACE2; as a genetically modified soluble form of ACE2 to compete with membranebound ACE2, and microRNAs (miRNAs); as a negative regulator of the expression of ACE2/TMPRSS2 to inhibit SARS-CoV2 entry into cells, are the potential therapeutic approaches discussed thoroughly in this article. This review provides the groundwork for the ongoing development of therapeutic agents and effective treatments against SARS-COV-2. K E Y W O R D S ACE2, COVID-19, drug repositioning, SARS-CoV-2, small molecule drugs 1 | INTRODUCTION SARS-CoV-2 is a single-stranded positive-sense RNA virus 1 that causes acute respiratory distress syndrome, which leads to serious global health issues. 2 The SARS-CoV in 2002-3, 3 the Mers-CoV in 2012-2013 4 and the current pandemic of SARS-CoV-2 prove that the diseases distribution is more expansive than previously recognized. 5 The glycosylated spike protein (S) is one of several structural proteins encodes by the COVID-19 genome. 6 This glycoprotein mediates virus entry by two functional subunits responsible for attachment to host cell receptor (S1 subunit) and viral and cellular membranes (S2 subunit) fusion. S is further cleaved at the S2 0 site, by a host transmembrane Serine Protease 2 (TMPRSS2), at immediate upstream of the fusion peptide. 7 The resulting cleavage leads to

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Actin blobs prefigure dendrite branching sites

Abstract: Nithianandam and Chien show via in vivo imaging that a dynamic population of F-actin termed actin blobs propagates bidirectionally in dendrites and stalls at future branching sites. The F-actin–severing protein Tsr/cofilin is a regulator of actin blob dynamics and dendrite branching.

Cited by 51 publications

References 82 publications

Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo

Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo

Distinct relations of microtubules and actin filaments with dendritic architecture

Potential COVID‐19 therapeutic approaches targeting angiotensin‐converting enzyme 2; An updated review

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