Microtubule-organizing centers: from the centrosome to non-centrosomal sites

Abstract

The process of cellular differentiation requires the distinct spatial organization of the microtubule cytoskeleton, the arrangement of which is specific to cell type. Microtubule patterning does not occur randomly, but is imparted by distinct subcellular sites called microtubule-organizing centers (MTOCs). Since the discovery of MTOCs fifty years ago, their study has largely focused on the centrosome. All animal cells use centrosomes as MTOCs during mitosis. However in many differentiated cells, MTOC function is reassigned to non-centrosomal sites to generate non-radial microtubule organization better suited for new cell functions, such as mechanical support or intracellular transport. Here, we review the current understanding of non-centrosomal MTOCs (ncMTOCs) and the mechanisms by which they form in differentiating animal cells.

Actin filaments regulate microtubule growth at the centrosome

“…The growth of the microtubule network and its architecture regulates cell polarization, migration and numerous key functions in differentiated cells (Mimori-Kiyosue, 2011;de Forges et al, 2012;Etienne-Manneville, 2013;Sanchez & Feldman, 2017). Microtubule growth first depends on microtubule nucleation, which is regulated by large complexes serving as microtubule templates and proteins that stabilize early protofilament arrangements (Wieczorek et al, 2015;Roostalu & Surrey, 2017).…”

Muscle Development: Nucleating Microtubules at the Nuclear Envelope

“…In myotubes, the cytoplasmic surface of the nuclear envelope serves as the major MTOC of the cell [4,5]. MTOC switching from a centrosome to a non-centrosomal location is a hallmark of differentiation [6]. An exciting report in this issue of Current Biology [7] characterizes the mechanisms for how the MTOC is recruited to the cytoplasmic surface of the nuclei in developing myotubes.…”

Intraflagellar transport 20 promotes collective cancer cell invasion by regulating polarized organization of Golgi‐associated microtubules

“…In osteosarcoma cells, IFT20 promotes nucleation of Golgi‐derived MTs . Accumulating evidence indicates that γ‐TuRC is involved in the nucleation of noncentrosomal MTs and/or anchoring their minus ends . A‐kinase anchor protein 450, a scaffolding protein localized at the centrosome and Golgi apparatus, can recruit γ‐TuRC to the cis ‐Golgi by interacting with a cis ‐Golgi matrix protein, GM130 .…”

“…4 Accumulating evidence indicates that γ-TuRC is involved in the nucleation of noncentrosomal MTs and/or anchoring their minus ends. 43,44 Akinase anchor protein 450, a scaffolding protein localized at the F I G U R E 3 Intraflagellar transport 20 (IFT20) is required for organization of Golgi-associated microtubules during collective invasion. A, DLD1 cells transfected with the indicated siRNAs were subjected to 2-D invasion assay for 18 h. Cells were stained with Abs against acetylated (Ac)-tubulin (green) and GM130 (red) and analyzed by super-resolution microscopy.…”