Periodic actin structures in neuronal axons are required to maintain microtubules

Qu, Yue; Hahn, Ines; Webb, S; Pearce, Simon P.; Prokop, Andreas

doi:10.1091/mbc.e16-10-0727

Cited by 100 publications

(138 citation statements)

References 79 publications

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“…Indeed, it has been shown that at least in the axon, periodic actin structures are required to maintain microtubules (Qu et al, 2017). That points to a very different nature and molecular environment of those two types of F-actin structures.…”

Section: Discussionmentioning

confidence: 99%

F‐actin patches associated with glutamatergic synapses control positioning of dendritic lysosomes

et al. 2019

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Organelle positioning within neurites is required for proper neuronal function. In dendrites, with their complex cytoskeletal organization, transport of organelles is guided by local specializations of the microtubule and actin cytoskeleton, and by coordinated activity of different motor proteins. Here, we focus on the actin cytoskeleton in the dendritic shaft and describe dense structures consisting of longitudinal and branched actin filaments. These actin patches are devoid of microtubules and are frequently located at the base of spines, or form an actin mesh around excitatory shaft synapses. Using lysosomes as an example, we demonstrate that the presence of actin patches has a strong impact on dendritic organelle transport, as lysosomes frequently stall at these locations. We provide mechanistic insights on this pausing behavior, demonstrating that actin patches form a physical barrier for kinesin‐driven cargo. In addition, we identify myosin Va as an active tether which mediates long‐term stalling. This correlation between the presence of actin meshes and halting of organelles could be a generalized principle by which synapses control organelle trafficking.

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Section: Discussionmentioning

confidence: 99%

F‐actin patches associated with glutamatergic synapses control positioning of dendritic lysosomes

et al. 2019

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“…The MPS can also act as a diffusion barrier and contribute to filtering membrane proteins at the axon initial segment (21). In addition, the MPS appears to affect the stability of microtubules in axons (22).…”

mentioning

confidence: 99%

Structural organization of the actin-spectrin–based membrane skeleton in dendrites and soma of neurons

Han

Zhou

Xia

et al. 2017

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

122

158

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Actin, spectrin, and associated molecules form a membraneassociated periodic skeleton (MPS) in neurons. In the MPS, short actin filaments, capped by actin-capping proteins, form ring-like structures that wrap around the circumference of neurites, and these rings are periodically spaced along the neurite by spectrin tetramers, forming a quasi-1D lattice structure. This 1D MPS structure was initially observed in axons and exists extensively in axons, spanning nearly the entire axonal shaft of mature neurons. Such 1D MPS was also observed in dendrites, but the extent to which it exists and how it develops in dendrites remain unclear. It is also unclear whether other structural forms of the membrane skeleton are present in neurons. Here, we investigated the spatial organizations of spectrin, actin, and adducin, an actin-capping protein, in the dendrites and soma of cultured hippocampal neurons at different developmental stages, and compared results with those obtained in axons, using superresolution imaging. We observed that the 1D MPS exists in a substantial fraction of dendritic regions in relatively mature neurons, but this structure develops slower and forms with a lower propensity in dendrites than in axons. In addition, we observed that spectrin, actin, and adducin also form a 2D polygonal lattice structure, resembling the expanded erythrocyte membrane skeleton structure, in the somatodendritic compartment. This 2D lattice structure also develops substantially more slowly in the soma and dendrites than the development of the 1D MPS in axons. These results suggest membrane skeleton structures are differentially regulated across different subcompartments of neurons.actin | spectrin | adducin | super-resolution imaging | STORM I t was recently discovered that actin, spectrin, and associated molecules form a membrane-associated periodic skeleton (MPS) structure in neurons (1). As revealed by superresolution stochastic optical reconstruction microscopy (STORM) (1), this structure contains molecules homologous to those present in the erythrocyte membrane skeleton, including spectrin (2-4), actin, and actincapping proteins such as adducin (5, 6), but adopts a structural organization that is distinct from the polygonal lattice structure of the erythrocyte membrane skeleton (7,8). In this structure, short actin filaments capped by adducin are organized into repetitive, ring-like structures that wrap around the circumference of the axon underneath the axonal membrane, and adjacent actin rings are connected by spectrin tetramers, forming a long-range quasi-1D periodic structure with a periodicity of ∼190 nm (1). This periodic structure is formed extensively throughout the axonal shaft, including the axon initial segment and the unmyelinated distal axons, as well as the nodes of Ranvier and internodal segments in myelinated axons (1, 9-14), but appears to be perturbed at synaptic sites (13,15,16). It is a highly prevalent structure observed in many different types of neurons, including both excitatory and inhibitory neuro...

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“…Less is known, however, about how such a cross-linked microtubule array is immobilized itself in the neuron. In Drosophila, the microtubule cytoskeleton is stabilized by the spectraplakin protein Shot, which binds to both microtubules and the actin cytoskeleton (Qu et al, 2017;Sanchez-Soriano et al, 2009). Although the role of Shot in setting up axon-dendrite polarity is not addressed, in the absence of Shot, axon regeneration is affected and the microtubules are less bundled, which leads to buckling of microtubules.…”

Section: Discussionmentioning

confidence: 99%

“…Various microtubule associated proteins (MAPs) bind to the microtubule lattice, which can stabilize the microtubule itself and can cross-link them together thus preventing microtubule-microtubule sliding (Bodakuntla et al, 2019). In addition, the microtubule bundles were found connected to other cortical cytoskeletal elements (Freal et al, 2016;Liang et al, 2013;Qu et al, 2017). Although the importance of cortical anchoring of microtubule bundles to maintain neuronal microtubule organization and thereby maintain neuronal polarity and function is apparent, the evidence for this is largely lacking.…”

Section: Introductionmentioning

confidence: 99%

Cortical anchoring of the microtubule cytoskeleton is essential for neuron polarity and functioning

Kooistra

Das

et al. 2019

Preprint

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Neurons are among the most highly polarized cell types. They possess structurally and functionally different processes, axon and dendrites, to mediate information flow through the nervous system.Although it is well known that the microtubule cytoskeleton has a central role in establishing neuronal polarity, how its specific organization is established and maintained is little understood.Using the in vivo model system Caenorhabditis elegans, we found that the highly conserved UNC-119 protein provides a link between the membrane-associated Ankyrin (UNC-44) and the microtubuleassociated CRMP (UNC-33). Together they form a periodic membrane-associated complex that anchors axonal and dendritic microtubule bundles to the cell cortex. This anchoring is critical to maintain microtubule organization by opposing kinesin-1 powered microtubule sliding. Disturbing this molecular complex alters neuronal polarity and causes strong developmental defects of the nervous system leading to severely paralyzed animals.

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Periodic actin structures in neuronal axons are required to maintain microtubules

Cited by 100 publications

References 79 publications

F‐actin patches associated with glutamatergic synapses control positioning of dendritic lysosomes

F‐actin patches associated with glutamatergic synapses control positioning of dendritic lysosomes

Structural organization of the actin-spectrin–based membrane skeleton in dendrites and soma of neurons

Cortical anchoring of the microtubule cytoskeleton is essential for neuron polarity and functioning

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