Compartmentalization within neurites: Its mechanisms and implications

Katsuki, Takeo; Joshi, Rajshri; Ailani, Deepak; Hiromi, Yasushi

doi:10.1002/dneu.20859

Cited by 12 publications

(10 citation statements)

References 87 publications

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“…For example, the microtubule cytoskeleton is organized differently in axons and dendrites, allowing distinct modes of trafficking (Baas et al, 1988;Horton and Ehlers, 2003). Beyond this basic level of compartmentalization, neurons display extreme diversity in axon and dendrite morphology, and both axons and dendrites contain structurally and functionally distinct subdomains (Katsuki et al, 2011;Masland, 2004).…”

Section: Introductionmentioning

confidence: 99%

Coordinate control of terminal dendrite patterning and dynamics by the membrane protein Raw

et al. 2015

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The directional flow of information in neurons depends on compartmentalization: dendrites receive inputs whereas axons transmit them. Axons and dendrites likewise contain structurally and functionally distinct subcompartments. Axon/dendrite compartmentalization can be attributed to neuronal polarization, but the developmental origin of subcompartments in axons and dendrites is less well understood. To identify the developmental bases for compartment-specific patterning in dendrites, we screened for mutations that affect discrete dendritic domains in Drosophila sensory neurons. From this screen, we identified mutations that affected distinct aspects of terminal dendrite development with little or no effect on major dendrite patterning. Mutation of one gene, raw, affected multiple aspects of terminal dendrite patterning, suggesting that Raw might coordinate multiple signaling pathways to shape terminal dendrite growth. Consistent with this notion, Raw localizes to branch-points and promotes dendrite stabilization together with the Tricornered (Trc) kinase via effects on cell adhesion. Raw independently influences terminal dendrite elongation through a mechanism that involves modulation of the cytoskeleton, and this pathway is likely to involve the RNA-binding protein Argonaute 1 (AGO1), as raw and AGO1 genetically interact to promote terminal dendrite growth but not adhesion. Thus, Raw defines a potential point of convergence in distinct pathways shaping terminal dendrite patterning.

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Section: Introductionmentioning

confidence: 99%

Coordinate control of terminal dendrite patterning and dynamics by the membrane protein Raw

et al. 2015

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“…RhoA activation may be restricted to the rear via the observed asymmetric flow; although in contrast Rac1, which moved equally well in all directions, is likely activated locally via spatial control of upstream signals. Previous work has suggested that actin and other cytoskeletal components form barriers to diffusion and accelerate cross-cell transport by restricting trafficking to particular pathways (11). pCF/ FLIM makes these pathways visible and will enable us to correlate localized activation with directed movement through specific subcellular regions.…”

Section: Discussionmentioning

confidence: 99%

Millisecond spatiotemporal dynamics of FRET biosensors by the pair correlation function and the phasor approach to FLIM

Hinde

Digman

Hahn

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Here we present a fluctuation-based approach to biosensor Förster resonance energy transfer (FRET) detection that can measure the molecular flow and signaling activity of proteins in live cells. By simultaneous use of the phasor approach to fluorescence lifetime imaging microscopy (FLIM) and cross-pair correlation function (pCF) analysis along a line scanned in milliseconds, we detect the spatial localization of Rho GTPase activity (biosensor FRET signal) as well as the diffusive route adopted by this active population. In particular we find, for Rac1 and RhoA, distinct gradients of activation (FLIM-FRET) and a molecular flow pattern (pCF analysis) that explains the observed polarized GTPase activity. This multiplexed approach to biosensor FRET detection serves as a unique tool for dissection of the mechanism(s) by which key signaling proteins are spatially and temporally coordinated. T o dissect the mechanism by which a signaling pathway is regulated it is necessary to not only measure the localization of the key signaling proteins, but also their activation at different subcellular locations. This is most often accomplished via the use of genetically encoded biosensors (1, 2). Given that the great majority of biosensor designs use a Förster resonance energy transfer (FRET) interaction as a report of the activity being probed, there is great interest in the development of methods for biosensor FRET detection with high spatial and temporal resolution (1). For example, in a recent study by Machacek and coworkers, the spatiotemporal coordination of several Rho GTPases was probed on the second and micrometer scale at the leading edge of migrating cells, via the use of a series of FRET biosensors (3). Edge velocity was correlated with the changing activation of GTPase biosensors in defined regions adjacent to the edge. This revealed correlations of RhoA, Rac1, and Cdc42 activity with leading-edge dynamics that had not previously been detected using static or low temporal resolution imaging. Along this line, in an even more recent study, Kunida et al. developed an image processing algorithm to extract the FRET values and velocities from an entire cell periphery (4). With this analytical approach they revealed several feedback regulations between Rac1 and membrane protrusion, which could not have been observed without use of a global field of view and high spatial resolution imaging (micrometer scale).Determination of biosensor FRET in cells at a quantitative level is thought to be best achieved using the quenching of the donor lifetime, which directly detects the "on" and "off" state of the FRET biosensor. We recently demonstrated this property by applying the phasor approach to fluorescence lifetime imaging (FLIM) on the GTPase biosensors used by Machacek and coworkers (5). Using a frame mode acquisition we were able to spatially map and quantify the degree of Rac1 and RhoA activation in each pixel of an image as a function of time, independent of other sources of fluorescence for both single-and dual-chain designs....

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“…). These findings raise intriguing questions on the development, maintenance, and function of these sub‐compartments (Katsuki et al, ).…”

Section: Introduction: Sub‐compartments In Neuronsmentioning

confidence: 99%

Neuronal sub‐compartmentalization: a strategy to optimize neuronal function

et al. 2019

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Neurons are highly polarized cells that consist of three main structural and functional domains: a cell body or soma, an axon, and dendrites. These domains contain smaller compartments with essential roles for proper neuronal function, such as the axonal presynaptic boutons and the dendritic postsynaptic spines. The structure and function of these compartments have now been characterized in great detail. Intriguingly, however, in the last decade additional levels of compartmentalization within the axon and the dendrites have been identified, revealing that these structures are much more complex than previously thought. Herein we examine several types of structural and functional sub‐compartmentalization found in neurons of both vertebrates and invertebrates. For example, in mammalian neurons the axonal initial segment functions as a sub‐compartment to initiate the action potential, to select molecules passing into the axon, and to maintain neuronal polarization. Moreover, work in Drosophila melanogaster has shown that two distinct axonal guidance receptors are precisely clustered in adjacent segments of the commissural axons both in vivo and in vitro, suggesting a cell‐intrinsic mechanism underlying the compartmentalized receptor localization. In Caenorhabditis elegans, a subset of interneurons exhibits calcium dynamics that are localized to specific sections of the axon and control the gait of navigation, demonstrating a regulatory role of compartmentalized neuronal activity in behaviour. These findings have led to a number of new questions, which are important for our understanding of neuronal development and function. How are these sub‐compartments established and maintained? What molecular machinery and cellular events are involved? What is their functional significance for the neuron? Here, we reflect on these and other key questions that remain to be addressed in this expanding field of biology.

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Compartmentalization within neurites: Its mechanisms and implications

Cited by 12 publications

References 87 publications

Coordinate control of terminal dendrite patterning and dynamics by the membrane protein Raw

Coordinate control of terminal dendrite patterning and dynamics by the membrane protein Raw

Millisecond spatiotemporal dynamics of FRET biosensors by the pair correlation function and the phasor approach to FLIM

Neuronal sub‐compartmentalization: a strategy to optimize neuronal function

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