Lumenal components of cytoplasmic microtubules

Abstract

The lumen of cytoplasmic microtubules is a poorly explored expanse of intracellular space. Although typically represented in textbooks as a hollow tube, studies over several decades have shown that the microtubule lumen is occupied by a range of morphologically diverse components. These are predominantly globular particles of varying sizes which appear to exist either in isolation, bind to the microtubule wall, or form discontinuous columns that extend through the lumenal space. Actin filaments with morphologies distinct from the canonical cytoplasmic forms have also now been found within the microtubule lumen. In this review, we examine the historic literature that observed these lumenal components in tissues from diverse species and integrate it with recent cryo-electron tomography studies that have begun to identify lumenal proteins. We consider their cell and tissue distribution, possible mechanisms of incorporation, and potential functions. It is likely that continuing work in this area will open a new frontier in cytoskeletal biology.

CryoET reveals actin filaments within platelet microtubules

“…In any case, the presence of these structures in HAP1 cell projections highlights the importance of considering intermediates on an assembly/disassembly pathway. This may be particularly important when examining morphologically diverse lumenal material in other cell types that has filamentous character but unknown composition 27 . Structural studies of Class II and Class III filaments are, therefore, a priority.…”

“…There are now many high-resolution imaging studies examining microtubules in their native environment that have not observed lumenal filaments but that have observed extensive particulate and globular lumenal material, for example, in neurons 31 , 32 and malaria parasites 33 , 34 , as well as others reviewed in ref. 27 . However, filamentous lumenal structures have recently been observed in fibroblasts grown in cell-derived matrices 35 .…”

How neurons maintain their axons long-term: an integrated view of axon biology and pathology

“…This requires dynamic changes of MT networks driven by processes of nucleation, de−/polymerisation, repair, posttranslational modification and cross-linkage, all mediated by MT-binding proteins (‘Eb, X, Sp, 11, 18’ in Figure 1 >a + b/m + n and e/g; some details further below; Conde and Caceres, 2009 ; Hahn et al, 2019 ; Janke and Magiera, 2020 ). MTs were also reported to contain proteins in their lumen which might regulate MT stability; these include actin filaments, MAP 6 and chaperones ( Cuveillier et al, 2020 ; Paul et al, 2020 ; Chakraborty et al, 2022 ; Tsuji and Dodding, 2022 ).…”

CryoET reveals actin filaments within platelet microtubules

“…In any case, the presence of these structures in HAP1 cell projections highlights the importance of considering intermediates on an assembly/disassembly pathway. This may be particularly important when examining morphologically diverse lumenal material in other cell types that has filamentous character but unknown composition [25]. Structural studies of Class II and Class III filaments are therefore a priority.…”