Biophysical and Quantitative Principles of Centrosome Biogenesis and Structure

Abstract

The centrosome is a main orchestrator of the animal cellular microtubule cytoskeleton. Dissecting its structure and assembly mechanisms has been a goal of cell biologists for over a century. In the last two decades, a good understanding of the molecular constituents of centrosomes has been achieved. Moreover, recent breakthroughs in electron and light microscopy techniques have enabled the inspection of the centrosome and the mapping of its components with unprecedented detail. However, we now need a profound and dynamic understanding of how these constituents interact in space and time. Here, we review the latest findings on the structural and molecular architecture of the centrosome and how its biogenesis is regulated, highlighting how biophysical techniques and principles as well as quantitative modeling are changing our understanding of this enigmatic cellular organelle. Expected final online publication date for the Annual Review of Cell and Developmental Biology, Volume 37 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Moonlighting at the Poles: Non-Canonical Functions of Centrosomes

“…Characterized as a protein-dense scaffolding structure responsible for the nucleation of α - and β -tubulin, centrosomes arrange and anchor microtubules that form the bipolar spindle in mitosis (reviewed in Wu and Akhmanova, 2017 ; Gomes Pereira et al, 2021 ) ( Figure 1 ). The main microtubule nucleator is the γ-tubulin ring complex (γ-TuRC), a highly conserved complex responsible for the capping of microtubule minus ends ( Oakley et al, 1990 ; Zheng et al, 1995 ).…”

“…Despite lacking a finite membrane border, the centrosome maintains its unique tri-dimensional shape via centrosome-interacting proteins, 500 of which have been identified to date ( Andersen et al, 2003 ; Gupta et al, 2015 ; Gheiratmand et al, 2019 ). Throughout the cell cycle, its size and composition vary, allowing for diverse arrangements in microtubule organization ( Devi et al, 2021 ; Gomes Pereira et al, 2021 ). Centrosomes contain centrioles, a pair of cylindrical organelles perpendicularly positioned to one another ( Figure 1A ).…”

Molecular architecture of the C. elegans centriole

“…This is followed by SAS-4 (CPAP in human) recruitment to the procentriole, a protein thought to enable the addition of microtubules to the SAS-6/SAS-5 scaffold. Relatives of SAS-7, SPD-2, ZYG-1, SAS-6, SAS-5 and SAS-4 in other systems are recruited in a similar sequence and exert analogous functions in procentriole formation (reviewed in [10][11][12]. SAS-6 is the main building block of a scaffold referred to as the cartwheel, which is thought to contribute to imparting the 9-fold radial symmetry of the organelle (14,15).…”

“…This is followed by SAS-4 (CPAP in human) recruitment to the procentriole, a protein thought to enable the addition of microtubules to the SAS-6/SAS-5 scaffold. Relatives of SAS-7, SPD-2, ZYG-1, SAS-6, SAS-5 and SAS-4 in other systems are recruited in a similar sequence and exert analogous functions in procentriole formation (reviewed in 10–12).…”

“…As in other systems, starting approximately at the onset of S phase, the two resident centrioles in C. elegans each seed the assembly of a procentriole in their vicinity, such that four centriolar units are present during mitosis, two per spindle pole. Comprehensive genetic and functional genomic screens conducted in C. elegans led to the discovery of six components essential for procentriole formation, which are largely conserved in overall structure and function across eukaryotic evolution (reviewed in [10][11][12]. Molecular epistasis experiments uncovered the order in which proteins essential for procentriole formation are recruited to the worm organelle (7,13).…”