Mechanisms of Polarized Organelle Distribution in Neurons

Current Opinion in Cell Biology, 2012

Encyclopedia of Neuroscience, 2009

Oxford Open Neuroscience

The initiation of nascent projections, or neurites, from the neuronal cell body is the first stage in the formation of axons and dendrites, and thus a critical step in the establishment of neuronal architecture and nervous system development. Neurite formation relies on the polarized remodelling of microtubules, which dynamically direct and reinforce cell shape, and provide tracks for cargo transport and force generation. Within neurons, microtubule behaviour and structure are tightly controlled by an array of regulatory factors. Although microtubule regulation in the later stages of axon development is relatively well understood, how microtubules are regulated during neurite initiation is rarely examined. Here, we discuss how factors that direct microtubule growth, remodelling, stability and positioning influence neurite formation. In addition, we consider microtubule organization by the centrosome and modulation by the actin and intermediate filament networks to provide an up-to-d...

Nature, 2005

Neuronal polarization occurs shortly after mitosis. In neurons differentiating in vitro, axon formation follows the segregation of growth-promoting activities to only one of the multiple neurites that form after mitosis 1,2 . It is unresolved whether such spatial restriction makes use of an intrinsic program, like during C. elegans embryo polarization 3 , or is extrinsic and cue-mediated, as in migratory cells 4 . Here we show that in hippocampal neurons in vitro, the axon consistently arises from the neurite that develops first after mitosis. Centrosomes, the Golgi apparatus and endosomes cluster together close to the area where the first neurite will form, which is in turn opposite from the plane of the last mitotic division. We show that the polarized activities of these organelles are necessary and sufficient for neuronal polarization: (1) polarized microtubule polymerization and membrane transport precedes first neurite formation, (2) neurons with more than one centrosome sprout more than one axon and (3) suppression of centrosome-mediated functions precludes polarization. We conclude that asymmetric centrosome-mediated dynamics in the early post-mitotic stage instruct neuronal polarity, implying that pre-mitotic mechanisms with a role in division orientation may in turn participate in this event.

Aside from rare counterexamples (e.g. the starburst amacrine cell in retina), neurons are polarized into two compartments, dendrites and axon, which are linked at the cell body. This structural polarization carries an underlying molecular definition and maps into a general functional polarization whereby inputs are collected by the dendrites and cell body, and output is distributed via the axon. Explanations of how the polarized structure arises invariably coalesce around somatic polarity, defined by the roving location of the microtubule organizing centre, or centrosome, the Golgi apparatus, associated endosomes and the nucleus during early development. In some neurons, proper positioning of these structures can determine the sites for axon and dendrite elongation, and support processes that underlie cell migration. We briefly review these events as a basis to propose a new role for polarized arrangement of somatic organelles as a potential determinant for patterned innervation of the cell body membrane. We cite an example from preliminary studies of synaptogenesis at the calyx of Held, a large nerve terminal that selectively innervates the cell body of its postsynaptic partner, and suggest other neural systems in which polarity mechanisms may guide initial synapse formation onto the somatic surface.

Journal of Cell Science, 2005

Fucus zygotes polarise and germinate a rhizoid before their first asymmetrical division. The role of microtubules (MTs) in orienting the first division plane has been extensively studied by immunofluorescence approaches. In the present study, the re-organisation of MT arrays during the development of Fucus zygotes and embryos was followed in vivo after microinjection of fluorescent tubulin. A dynamic cortical MT array that shows dramatic reorganization during zygote polarization was detected for the first time. Randomly distributed cortical MTs were redistributed to the presumptive rhizoid site by the time of polarisation and well before rhizoid germination. The cortical MT re-organisation occurs independently of centrosome separation and nucleation. By the time of mitosis the cortical array depolymerised to cortical foci in regions from which it also reformed following mitosis, suggesting that it is nucleated from cortical sites. We confirm previous indications from immunodetection...

Neuroscience, 1993

Scientific Reports

Axonal microtubules are more stable than those in the remaining neurites, while dynamics of F-actin in axonal growth cones clearly exceed those in their dendritic counterparts. However, whether a functional interplay exists between the microtubule network and F-actin dynamics in growing axons and whether this interplay is instrumental for breaking cellular symmetry is currently unknown. Here, we show that an increment on microtubule stability or number of microtubules is associated with increased F-actin dynamics. Moreover, we show that Drebrin E, an F-actin and microtubule plusend binding protein, mediates this cross talk. Drebrin E segregates preferentially to growth cones with a higher F-actin treadmilling rate, where more microtubule plus-ends are found.

Nature Communications, 2016

Neurons display a highly polarized microtubule network that mediates trafficking throughout the extensive cytoplasm and is crucial for neuronal differentiation and function. In newborn migrating neurons, the microtubule network is organized by the centrosome. During neuron maturation, however, the centrosome gradually loses this activity, and how microtubules are organized in more mature neurons remains poorly understood. Here, we demonstrate that microtubule organization in post-mitotic neurons strongly depends on non-centrosomal nucleation mediated by augmin and by the nucleator gTuRC. Disruption of either complex not only reduces microtubule density but also microtubule bundling. These microtubule defects impair neurite formation, interfere with axon specification and growth, and disrupt axonal trafficking. In axons augmin does not merely mediate nucleation of microtubules but ensures their uniform plus end-out orientation. Thus, the augmin-gTuRC module, initially identified in mitotic cells, may be commonly used to generate and maintain microtubule configurations with specific polarity.

Nature Reviews Neuroscience, 2009

The region of a cell that lies beneath the plasma membrane and contains a network of actin filaments and associated proteins. The interaction between microtubules and components of the cell cortex that results in stabilization of the microtubules.