Functions and dysfunctions of the mammalian centrosome in health, disorders, disease, and aging.

Abstract

Since its discovery well over 100years ago (Flemming, in Sitzungsber Akad Wissensch Wien 71:81-147, 1875; Van Beneden, in Bull Acad R Belg 42:35-97, 1876) the centrosome is increasingly being recognized as a most impactful organelle for its role not only as primary microtubule organizing center (MTOC) but also as a major communication center for signal transduction pathways and as a center for proteolytic activities. Its significance for cell cycle regulation has been well studied and we now also know that centrosome dysfunctions are implicated in numerous diseases and disorders including cancer, Alstrom syndrome, Bardet-Biedl syndrome, Huntington's disease, reproductive disorders, and several other diseases and disorders. The present review is meant to build on information presented in the previous review (Schatten, in Histochem Cell Biol 129:667-686, 2008) and to highlight functions of the mammalian centrosome in health, and dysfunctions in disorders, disease, and aging with six sections focused on (1) centrosome structure and functions, and new insights into the role of centrosomes in cell cycle progression; (2) the role of centrosomes in tumor initiation and progression; (3) primary cilia, centrosome-primary cilia interactions, and consequences for cell cycle functions in health and disease; (4) transitions from centrosome to non-centrosome functions during cellular polarization; (5) other centrosome dysfunctions associated with the pathogenesis of human disease; and (6) centrosome functions in oocyte germ cells and dysfunctions in reproductive disorders and reproductive aging.