Cellular cartography: Towards an atlas of the neuronal microtubule cytoskeleton

Abstract

Microtubules, one of the major components of the cytoskeleton, play a crucial role during many aspects of neuronal development and function, such as neuronal polarization and axon outgrowth. Consequently, the microtubule cytoskeleton has been implicated in many neurodevelopmental and neurodegenerative disorders. The polar nature of microtubules is quintessential for their function, allowing them to serve as tracks for long-distance, directed intracellular transport by kinesin and dynein motors. Most of these motors move exclusively towards either the plus- or minus-end of a microtubule and some have been shown to have a preference for either dynamic or stable microtubules, those bearing a particular post-translational modification or those decorated by a specific microtubule-associated protein. Thus, it becomes important to consider the interplay of these features and their combinatorial effects on transport, as well as how different types of microtubules are organized in the cell. Here, we discuss microtubule subsets in terms of tubulin isotypes, tubulin post-translational modifications, microtubule-associated proteins, microtubule stability or dynamicity, and microtubule orientation. We highlight techniques used to study these features of the microtubule cytoskeleton and, using the information from these studies, try to define the composition, role, and organization of some of these subsets in neurons.

Aurora B controls microtubule stability to regulate abscission dynamics in stem cells

“…Stable microtubules are less sensitive to mechanical stress (76), thus stable microtubules could promote the structural integrity of the bridge. Interestingly, stable microtubules (which we demonstrate hinder abscission) are generally polyglutamylated (77) and polyglutamylation modulates spastin activity (78). In sum, our data suggest that abscission dynamics could depend on the regulation of spastin activity by microtubule stability.…”

Light-induced trapping of endogenous proteins reveals spatiotemporal roles of microtubule and kinesin-1 in dendrite patterning ofDrosophilasensory neurons

“…MT-based transport plays critical roles in dendrite growth and patterning. The (+) end-directed motor kinesin and the (-) end-directed motor dynein work in concert to transport cargos needed for branch growth to proper locations within the dendritic arbor (Iwanski and Kapitein, 2023; Kelliher et al, 2019). LOF of kinesin and dynein in C4da neurons results in very similar phenotypes of shifting of high-order dendrites towards the cell body (proximal shift) (Satoh et al, 2008; Zheng et al, 2008), suggesting that certain “branching machinery” relies on the motor system for delivery to the distal dendritic arbor.…”

“…Although MTs are known to be important for neuronal morphogenesis (Iwanski and Kapitein, 2023; Kelliher et al, 2019), how MTs support the growth of highly dynamic dendritic branches is unclear. Because it is difficult to detect MTs in dynamic terminal dendrite branches, investigating the local role of MTs in dynamic dendrites has been challenging.…”

“…This caveat is particularly limiting for studying proteins that play multiple roles in different parts of the cell or at different stages of differentiation. An example is the microtubule (MT) cytoskeleton, which provides mechanical support to neuronal branches and serves as tracks for motor-based cargo transport (Iwanski and Kapitein, 2023; Kelliher et al, 2019). MT assembly, organization, and dynamics are important for dendrite growth and maintenance (Conde and Caceres, 2009), and MT-based motors, including kinesin and dynein, are important for neuronal polarity and dendrite patterning (Delandre et al, 2016).…”

A voyage from the ER: spatiotemporal insights into polarized protein secretion in neurons

“…The correct sorting of proteins from the ER to the plasma membrane (PM) is organized in multiple steps in which they are concentrated and packaged into different vesicle populations. The cytoskeletal network and the motors that move cargoes and organelles across it have been reviewed (Aiken and Holzbaur, 2021;Koppers and Farías, 2021;Iwanski and Kapitein, 2023). Here, we will focus on the sorting of cargoes within the secretory pathway and the transfer of proteins between membranous organelles.…”