SAK/PLK4 Is Required for Centriole Duplication and Flagella Development

Abstract

SAK/PLK4 is necessary for centriole duplication both in Drosophila and human cells. Drosophila cells tolerate the lack of centrioles and undertake mitosis but cannot form basal bodies and hence flagella. Human cells depleted of SAK show error-prone mitosis, likely to underlie its tumor-suppressor role.

Quantitative analysis of human centrosome architecture by targeted proteomics and fluorescence imaging

“…Centriole formation is initiated by the protein kinase Plk4 (also known as Sak; Bettencourt‐Dias et al , 2005; Habedanck et al , 2005), which undergoes activation through trans‐autophosphorylation at a T‐loop residue (Lopes et al , 2015). Steady‐state cellular levels of Plk4 are generally kept low through trans‐autophosphorylation of a DSG‐motif and subsequent degradation by SCF‐β‐TrCP (Guderian et al , 2010; Holland et al , 2010).…”

“…Centriole biogenesis and maintenance of correct centrosome numbers in proliferating cells critically depend on the exact levels of the key duplication factors Plk4 (Bettencourt‐Dias et al , 2005; Habedanck et al , 2005), Sas‐6 (Leidel et al , 2005; Strnad et al , 2007), and STIL (Tang et al , 2011b; Arquint et al , 2012; Vulprecht et al , 2012). To fully understand the regulation of centriole duplication, it will thus be important to obtain quantitative data on the abundance of these proteins under physiological conditions.…”

The Coordination between DNA Replication Initiation and Other Cell Cycle Events

“…Several proteins possibly function in the licensing process of centrosome duplication. Overexpression of Plk4, nucleophosmin (NPM/B23) and SAS-6 leads to centrosome amplification (Bettencourt-Dias et al 2005, Habedanck et al 2005, Leidel et al 2005, Dammermann et al 2004). The expression level of the Plk4 protein peaks at mitosis and is minimal in the G1 phase (Fode, Binkert and Dennis 1996).…”

Mitosis: wisdom, knowledge, and information

“…Another mechanism, known as the chromatin pathway, was originally identified in acentrosomal Xenopus meiotic oocytes and shown to involve the formation of a RanGTP gradient around chromosomes that promotes the nucleation of microtubules, which are subsequently organized into a bipolar structure by motor proteins [8]. Curiously, animal somatic cells that normally have centrosomes were shown to form a functional spindle after genetic or physical removal of centrosomes [9][10][11][12], indicating that a centrosome-4 independent pathway for spindle assembly exists in animal cells. However, the underlying molecular and structural requirements behind acentrosomal spindle formation in animal somatic cells remain largely unknown.…”