Microtubule Organization and Microtubule-Associated Proteins (MAPs)

Abstract

Dendrites have a unique microtubule organization. In vertebrates, dendritic microtubules are organized in antiparallel bundles, oriented with their plus ends either pointing away or toward the soma. The mixed microtubule arrays control intracellular trafficking and local signaling pathways, and are essential for dendrite development and function. The organization of microtubule arrays largely depends on the combined function of different microtubule regulatory factors or generally named microtubule-associated proteins (MAPs). Classical MAPs, also called structural MAPs, were identified more than 20 years ago based on their ability to bind to and copurify with microtubules. Most classical MAPs bind along the microtubule lattice and regulate microtubule polymerization, bundling, and stabilization. Recent evidences suggest that classical MAPs also guide motor protein transport, interact with the actin cytoskeleton, and act in various neuronal signaling networks. Here, we give an overview of microtubule organization in dendrites and the role of classical MAPs in dendrite development, dendritic spine formation, and synaptic plasticity. IntroductionMicrotubules (MTs) are cytoskeletal structures that play essential roles in all eukaryotic cells. MTs are important not only during cell division but also in non-dividing cells, where they are critical structures in numerous cellular processes such as cell motility, migration, differentiation, intracellular transport and organelle positioning. MTs are composed of two proteins, α-and β-tubulin, that form heterodimers and organize themselves in a head-to-tail manner. MTs are dynamic and they can rapidly switch between cycles of growth and shrinkage. This MT

Local Nucleation of Microtubule Bundles through Tubulin Concentration into a Condensed Tau Phase

“…Tau is known to localize to microtubule bundles in vivo, suggesting a role in organizing microtubule bundles. Although the mouse knockout of tau shows little phenotype, the double-knockout Tau/MAP1b has severe phenotypes ( Takei et al, 2000 ; Tortosa et al, 2016 ) and the deletion of tau results in upregulation of another MAP, MAP2, suggesting a compensatory mechanism ( Ma et al, 2014 ). A manuscript under review looking at the expression of GFP-tau constructs in neurons suggests that they also form higher-order assemblies in vivo (S.W., B. Eftekharzadeh, K. Tepper, K.M.…”

Microtubule-Associated Proteins: Structuring the Cytoskeleton

“…Given the large number of functions performed by MAPs, it is not surprising that they are also involved in various pathological conditions (reviewed in [136] [34,144,145], and research has focussed on tau aggregation as the key event in their pathogenesis. However, it is likely that the initial events are rather early perturbations of the physiological functions of MAPs.…”

“…A complex regulatory network coupling the tubulin code to a hypothetical MAP code could thus create a broad variety of microtubule identities that coordinate cytoskeletal functions in cells. Indeed, different MAPs show distinct subcellular localisations in neurons, which correlates with their specific contributions to a variety of neuronal functions [136].…”

Local Nucleation of Microtubule Bundles Through Tubulin Concentration Into a Condensed Tau Phase

“…Tau is known to localize to microtubule bundles in vivo, suggesting a role in organizing microtubule bundles. Although the mouse knockout of tau shows little phenotype, the double-knockout Tau/MAP1b has severe phenotypes (Takei et al, 2000;Tortosa et al, 2016) and the deletion of tau results in upregulation of another MAP, MAP2, suggesting a compensatory mechanism (Ma et al, 2014). A manuscript under review looking at the expression of GFP-tau constructs in neurons suggests that they also form higher-order assemblies in vivo (S.W., B.…”