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Mechanisms of microtubule organization in differentiated animal cells

Abstract

Microtubules are polarized cytoskeletal filaments that serve as tracks for intracellular transport and form a scaffold that positions organelles and other cellular components and modulates cell shape and mechanics. In animal cells, the geometry, density and directionality of microtubule networks are major determinants of cellular architecture, polarity and proliferation. In dividing cells, microtubules form bipolar spindles that pull chromosomes apart, whereas in interphase cells, microtubules are organized in a cell type-specific fashion, which strongly correlates with cell physiology. In motile cells, such as fibroblasts and immune cells, microtubules are organized as radial asters, whereas in immotile epithelial and neuronal cells and in muscles, microtubules form parallel or antiparallel arrays and cortical meshworks. Here, we review recent work addressing how the formation of such microtubule networks is driven by the plethora of microtubule regulatory proteins. These include proteins that nucleate or anchor microtubule ends at different cellular structures and those that sever or move microtubules, as well as regulators of microtubule elongation, stability, bundling or modifications. The emerging picture, although still very incomplete, shows a remarkable diversity of cell-specific mechanisms that employ conserved building blocks to adjust microtubule organization in order to facilitate different cellular functions.

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Fig. 1: Microtubule-organizing centres found in differentiated animal cells.
Fig. 2: Regulation of microtubule growth and stabilization.
Fig. 3: Microtubule sliding and reorientation.
Fig. 4: Microtubule organization in major mammalian cell types.

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The authors contributed equally to all aspects of the article.

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Glossary

Centrosome

A non-membranous organelle which consists of two centrioles surrounded by a proteinaceous matrix that nucleates and anchors microtubules.

Axon

A neuronal compartment that transmits signals.

Dendrites

Neuronal compartments that receive signals.

Centrioles

Cylindrical structures with a core of nine microtubule triplets. A centrosome contains two orthogonally arranged centrioles, the mother and the daughter centriole. A mother centriole is assembled one cell cycle earlier than the daughter centriole.

Condensates

Membraneless structures which can form by the physical process of liquid–liquid phase separation, whereby a well-mixed solution of macromolecules such as proteins or nucleic acids spontaneously separates into two phases, a dense phase and a dilute phase.

Axoneme

A microtubule-based cytoskeletal structure that forms the core of a cilium or a flagellum; it contains nine microtubule doublets, and in motile cilia also a central pair of microtubules

End binding proteins

(EBs). Conserved proteins that specifically bind to growing microtubule ends because they preferentially associate with the microtubule lattice in which β-tubulin is bound to GTP.

Dendritic arborization neurons

Neurons of a larval sensory type in Drosophila with specific dendritic morphologies.

Radial glial cells

Progenitor cells responsible for producing neurons of the cerebral cortex.

Oligodendrocytes

Myelinating glia cells of the central nervous system.

Growth cone

An actin-supported extension of a developing or regenerating axon or dendrite.

Fat body

An insect organ distributed throughout the body that has an essential role in energy storage and utilization.

Adherens junctions

Protein assemblies at cell–cell junctions in epithelial and endothelial cells; they contain transmembrane proteins called cadherins and are linked to the actin cytoskeleton.

Desmosomes

Adhesive protein complexes localized to intercellular junctions, responsible for maintaining the mechanical integrity of tissues.

Presynaptic boutons

Neurotransmitter-producing knoblike enlargements at the end of an axon involved in forming a synapse with another neuron.

Immunological synapse

The interface between an antigen-presenting cell or a target cell and a lymphocyte, such as a B cell or T cell, or a natural killer cell.

Catastrophes

Abrupt transitions from microtubule growth to shortening associated with loss of a GTP cap; they can occur spontaneously or be triggered by obstacles to microtubule growth or different cellular factors.

Rescues

Abrupt transitions from microtubule shortening to growth associated with regaining a GTP cap; these events are thought to be induced by cellular factors.

Axon initial segment

A plasma membrane-associated compartment at the base of an axon, which generates and shapes the action potential.

Focal adhesions

Integrin-containing multi-protein assemblies that establish mechanical links between intracellular actin bundles and the extracellular matrix.

Z-discs

Fine dense lines forming sarcomere boundaries, which stabilize actin filaments and allow force transmission between sarcomeres.

Sarcomeres

Basic contractile units of a muscle fibre; they contain actin and myosin filaments.

Gap junction

A channel that physically connects adjacent cells, mediating rapid exchange of small molecules.

Cytoplasmic streaming

Intracellular movement of the fluid substance (cytoplasm), transporting nutrients, macromolecules and organelles.

Dendritic spines

Membranous protrusions from a neuronal dendrite that receive input from an axon at the synapse.

Dendritic cells

Antigen-presenting cells that form an important role in the adaptive immune system.

mTORC1

(Mammalian (or mechanistic) target of rapamycin complex 1). A protein complex that functions as a nutrient, energy and redox sensor and controls protein synthesis.

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Akhmanova, A., Kapitein, L.C. Mechanisms of microtubule organization in differentiated animal cells. Nat Rev Mol Cell Biol 23, 541–558 (2022). https://doi.org/10.1038/s41580-022-00473-y

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  • DOI: https://doi.org/10.1038/s41580-022-00473-y

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