A non-canonical function of Plk4 in centriolar satellite integrity and ciliogenesis through PCM1 phosphorylation
Akiko Hori1,2, Karin Barnouin3, Ambrosius P Snijders3 andTakashi Toda1,4,*
EMBO Reports (2016) 17: 326–337
Speaker :Ting-Yu Chen 陳亭羽 Commentator: Prof.Chia-Yih Wang 王家義老師
Date: 2017/04/25 16:00-16:50 Location: Room 602
The centrosome is consisted of two centrioles, mother centriole and daughter centriole, and surrounded by pericentriolar material (PCM). Centrosome play a role as a microtubule-organizing center (MTOC) and build cell skeleton which are important for many cellular processes. Centriole duplication is important for cell cycle progression, and as the defect of centriole duplication leads many human diseases such as cancer and brain diseases. It has been known Serine/threonine-protein kinase Plk4 also known as polo-like kinase 4 is a master regulator of initial cartwheel formation during centriole duplication. Aberrant expression of Plk4 leads abnormal centriole copy numbers; when Plk4 malfunction, centriole fails to duplicate; when Plk4 overproduce, centriole undergo over amplification. Plk4 is important for centriole copy number control. In addition to Plk4, centriolar satellite also plays a role in controlling centriole duplication. Centriolar satellite, which is composed of PCM1, Cep295 and other proteins, scatters around the centrosome and facilitates cargo transport for promoting centrosome duplication. Thus, defects in centriolar satellite structure leads to poor centrosome duplication. Although Plk4 is essential for centriole duplication, it is unknown whether Plk4 plays any roles in centriolar satellite integrity. Here, the authors shows Plk4 is required for centriolar satellite organization and ciliogenesis. They prove depletion of Plk4 leads the dispersion of centriolar satellite and the defect of primary cilia. Plk4 interacts with centriolar satellite cargo protein, PCM1, and its kinase activity is required for PCM1 phosphorylation at S372 site. They show that nonphosphorylatable PCM1 mutant induces the same phenotype of Plk4 depletion and phosphomimetic mutant rescues the dispersion of centriolar satellite integrity and ciliogenesis in the PCM1-depleted cells. In addition, S372 phosphorylation site plays a role in PCM1 dimerization and interaction with other centriolar satellite components. According to these data, they suggestPlk4 mediates centriolar satellite integrity and ciliagenesis via PCM1 phosphorylation.