The Centrosome as a Geometry Organizer.

'Does the geometric design of centrioles imply their function? Several principles of construction of a microscopically small device for locating the directions of signal sources in microscopic dimensions: it appears that the simplest and smallest device that is compatible with the scrambling influence of thermal fluctuations, as are demonstrated by Brownian motion, is a pair of cylinders oriented at right angles to each other. Centrioles locate the direction of hypothetical signals inside cells' (Albrecht-Buehler G, Cell Motil, 1:237-245; 1981).Despite a century of devoted efforts (articles on the centrosome always begin like this) its role remains vague and nebulous: does the centrosome suffer from bad press? Likely it does, it has an unfair image problem. It is dispensable in mitosis, but a fly zygote, artificially deprived of centrosomes, cannot start its development; its sophisticated architecture (200 protein types, highly conserved during evolution) constitutes an enigmatic puzzle; centrosome reduction in gametogenesis is a challenging brainteaser; its duplication cycle (only one centrosome per cell) is more complicated than chromosomes. Its striking geometric design (two ninefold symmetric orthogonal centrioles) shows an interesting correspondence with the requirements of a cellular compass: a reference system organizer based on a pair of orthogonal goniometers; through its two orthogonal centrioles, the centrosome may play the role of a cell geometry organizer: it can establish a finely tuned geometry, inherited and shared by all cells. Indeed, a geometrical and informational primary role for the centrosome has been ascertained in Caenorhabditis elegans zygote: the sperm centrosome locates its polarity factors. The centrosome, through its aster of microtubules, possesses all the characteristics necessary to operate as a biophysical geometric compass: it could recognize cargoes equipped with topogenic sequences and drive them precisely to where they are addressed (as hypothesized by Albrecht-Buehler nearly 40 years ago). Recently, this geometric role of the centrosome has been rediscovered by two important findings; in the Kupffer's vesicle (the laterality organ of zebrafish), chiral cilia orientation and rotational movement have been described: primary cilia, in left and right halves of the Kupffer's vesicle, are symmetrically oriented relative to the midline and rotate in reverse direction. In mice node (laterality organ) left and right perinodal cells can distinguish flow directionality through their primary cilia: primary cilium, ninefold symmetric, is strictly connected to the centrosome that is located immediately under it (basal body). Kupffer's vesicle histology and mirror behaviour of mice perinodal cells suggest primary cilia are enantiomeric geometric organelles. What is the meaning of the geometric design of centrioles and centrosomes? Does it imply their function?

Integration of intracellular signaling: Biological analogues of wires, processors and memories organized by a centrosome 3D reference system.

BACKGROUND: Myriads of signaling pathways in a single cell function to achieve the highest spatio-temporal integration. Data are accumulating on the role of electromechanical soliton-like waves in signal transduction processes. Theoretical studies strongly suggest feasibility of both classical and quantum computing involving microtubules. AIM: A theoretical study of the role of the complex composed of the plasma membrane and the microtubule-based cytoskeleton as a system that transmits, stores and processes information. METHODS: Theoretical analysis presented here refers to (i) the Penrose-Hameroff theory of consciousness (Orchestrated Objective Reduction; Orch OR), (ii) the description of the centrosome as a reference system for construction of the 3D map of the cell proposed by Regolini, (iii) the Heimburg-Jackson model of the nerve pulse propagation along axons' lipid bilayer as soliton-like electro-mechanical waves. RESULTS AND CONCLUSION: The ideas presented in this paper provide a qualitative model for the decision-making processes in a living cell undergoing a differentiation process. OUTLOOK: This paper paves the way for the real-time live-cell observation of information processing by microtubule-based cytoskeleton and cell fate decision making.

Centrosome: is it a geometric, noise resistant, 3D interface that translates morphogenetic signals into precise locations in the cell?

The requirements of a spherical reference system based on two orthogonal goniometers show a surprising correspondence with the evidence emerging from numerous experimental studies on centrioles and centrosomes: the centrosome, because of the 9-fold symmetry of its centrioles, their orthogonal arrangement and their circumferential polarity, may play the role of an interface, composed by two orthogonal goniometers, that recognizes and decodes morphogenetic instructions, or, more generally, geometric molecular signals and translates them into their expected real locations in the cell. The purpose of this study is to outline a theoretical model of the centrosome and address the question on "how" the centrosome works, rather than investigate "what" centrioles might be or "what" might be their task, as many in-depth previous studies have discussed; the present analysis looks for the correspondence between structure and function in the centrosome, delineates a link between morphogenetic (DNA) instructions and their translation into actual locations into cells, tissues and organs, and finally analyzes centrosome behavior in many developmental processes: polarization, planar polarity, apical constriction, migration, morphogens transport, convergent extension, left-right bilateral symmetry and asymmetry establishment.