Microtubules and CAMSAP2

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In this image of the month we focus on the microtubules and the protein CAMSAP2. Microtubules are filaments that, together with the other components of the cytoskeleton, provide structure and shape to our cells. They also play important roles in intracellular transport, cell division, as well as the formation of cilia and flagella. Microtubules are formed by the polymerization and lateral association of alpha - and beta-tubulin proteins into a hollow tubelike filament. Due to the end-to-end linear arrangement of the α- and β-tubulin dimers the filaments have a polarity, which is crucial for their dynamics and their biological functions ( Akhmanova and Steinmetz, 2015).

There are quite many proteins that bind specifically to the plus ends of microtubules, where β-subunits are exposed. These are often involved in the regulation of microtubule dynamics. Far fewer proteins that bind to the minus-ends of microtubules, where α-subunits are exposed, have been found. The minus-ends are less dynamic but plays a crucial role in organizing the microtubule network in a cell-type specific manner ( Akhmanova and Steinmetz, 2019). One of them is called CAMSAP2 ( Jiang et al, 2014), which you can see associated with microtubule ends in the subcellular section of the HPA.

Microtubule polymerization is generally initiated from the gamma-tubulin ring complex (γ -TuRC) found at microtubule organizing centers (MTOCs), like the centrosome or basal body. In mesenchymal cells, the minus ends of most microtubules remain anchored to the centrosome, while the plus ends radiate towards the periphery of the cell, creating a network that extends from the centrosome. However, in highly polarized cells such as neurons, muscle cells and epithelial cells, microtubules can be arranged in completely different ways. The specialized organization of microtubule arrays in such cells is crucial for the polarized arrangement of cell components, which is in turn fundamental for their specialized cell functions.

Non-centrosomal arrangements can be achieved by detachment of microtubules from the centrosome, severing of existing microtubules or non-centrosomal assembly of microtubules. CAMSAP2 and other minus-end binding proteins are known to stabilize the free minus ends ( Atherton et al, 2017). Rather recently, it was shown that CAMSAP2 also can promote nucleation of microtubule polymerization independent of (γ -TuRC, possibly mediating nucleation outside of centrosomes ( Imasaki et al, 2022). In this case, CAMSAP2 seem to do so by bringing soluble αβ-tubulin dimers together in condensates by a process called phase-separation, promoting polymerization by bridging dimers together, and stabilizing newly formed filaments.