Microtubules carry out diverse roles within neurons.

Microtubules carry out diverse roles within neurons.

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Neurons are exquisitely polarized cells whose structure and function relies on microtubules. Microtubules in signal-receiving dendrites and signal-sending axons differ in their organization and microtubule-associated proteins. These differences, coupled with microtubule post-translational modifications, combine to locally regulate intracellular tra...

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... neuronal microtubule cytoskeleton shapes and supports the axonal and dendritic projections that carry out the distinct functions of signal reception and transmission. Microtubules in axons and dendrites are distinguished by their polarity, organization, posttranslational modifications, and microtubule-binding proteins ( Figure 1). Microtubules have an intrinsic polarity due to the head-to-tail assembly of α-and β-tubulin dimers (the β-and α-tubulin ends are referred to as the plus-and minus-ends, respectively). ...
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... motors and other proteins read-out this polarity, which is thought to be a central underpinning of neuronal polarity. In axons, microtubules are uniformly arrayed with their plus-end positioned distal towards the axon terminal, whereas in dendrites, microtubule polarity is mixed to varying degrees depending on position within the dendritic arbor, neuronal type, and organism ( Figure 1A). Microtubule orientation is regulated in part by the molecular motors dynein and kinesin, which play key roles in constructing the tracks that they use for transport [1][2][3][4][5]. ...
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... microtubule acetylation by either mutating α-tubulin K40 or deleting the modifying enzyme α-tubulin acetyltransferase 1 (αTAT1) does not cause lethality but does impair touch sensitivity [24]. Two recent studies point to the mechanistic roles that acetylated microtubules may play in mechanosensation ( Figure 1B). Touch and other mechanical stimuli trigger ion channel opening when force is exerted on a neuronal membrane. ...
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... patterning of microtubules by different combinations of PTMs as well as tubulin isotypes is referred to as the "tubulin code" [23,42]. Recent work has revealed a striking correlation between microtubule polarity and the tubulin code in the dendrites of cultured hippocampal neurons [43] (Figure 1 ). "Motor-paint," super-resolution microscopy coupled with motor particle tracking, showed that dendritic microtubules of the same polarity are bundled together, marked with distinctive PTMs, and are preferred tracks for different motor families. ...
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... is microtubule trafficking locally regulated to mediate dendritic function? In hippocampal neurons, growing microtubules have been caught transiently entering dendritic spines, the actin-enriched protrusions that contain excitatory synapses [55][56][57] (Figure 1D). These polymerizing microtubules are used by kinesin-3 to carry synaptotagmin IV, which regulates exocytosis, into spines via a so-called "direct deposit" mechanism [58]. ...
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... hippocampal axons, the proximal axon is divided into two zones, a preaxonal exclusion zone and axon initial segment (AIS), both of which regulate cargo entry. To exclude dendritic cargo, the dynein cofactor Ndel1, which is enriched at the AIS, "catches" dendritic cargo and transfers the cargo to dynein for transport to dendrites [63] (Figure 1E). The fly ortholog of Ndel1, NudE, likely carries out a similar role in restricting the entry of Golgi into axons [64]. ...
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... proper targeting of a cargo depends on the coordination of motor activity, in particular the coordination of motors that pull cargos towards opposite ends of a microtubule. In the proximal axon of mammalian sensory neurons, MAP2 inhibits kinesin-1 but not kinesin-3, hence restricting the entry of dense core vesicles (DCVs) that are not bound by both motors [66] (Figure 1D). Once DCVs have made it past the proximal axon, the motors coordinate their activity for efficient transport to the axon terminal [66,67]. ...

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... This raises the intriguing possibility that it represents a neuroprotective mechanism designed to limit viral spread, as proposed previously (Mukherjee et al., 2013;Sundaramoorthy et al., 2020). Neuronal processes, especially axons, are highly reliant on microtubule-dependent transport for function and survival (De Vos et al., 2008;Magiera et al., 2018;Guedes-Dias and Holzbaur, 2019;Kelliher et al., 2019;Koppers and Farías, 2021), and several neurotropic viruses including Theiler's virus, herpes simplex virus, poliovirus, rabies virus, and West Nile virus (WNV), transit in axons, likely relying on microtubule-dependent transport to reach their targets (Salinas et al., 2009 andreviewed in Richards et al., 2021). Thus, the significant increase in infection and death of neuronal somas in SARM1-depleted cultures (with delayed degeneration of neuronal processes) suggests that ZIKV can be transported in this way too and that SARM1-dependent degeneration of neuronal processes limits its spread to neuronal somas. ...
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... Neuronal MTs are arranged in a specific orientation [9,69]. In axons, MTs have an almost exclusive plus-end-out orientation, whereas in dendrites, MTs have an antiparallel organization with equal proportions of plus-end and minus-end towards the soma [70]. ...
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... FKBP52 is partially associated with the MT network in different cell types sugges an implication in MT function [30]. MTs are key cytoskeletal components that pla important role in neuronal architecture, intracellular trafficking and signa [73,74].They are highly regulated and possess a dynamic character allowing them continuously migrate through the cytoplasm. Originally discovered in association steroid hormone receptors (SHR), FKBP52 is involved in endocrine signaling in a dependent manner [75][76][77]. ...
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