Centrioles are 9-fold symmetric structures duplicating once per cell cycle. Duplication involves self-oligomerization of the centriolar protein SAS-6, but how the 9-fold symmetry is invariantly established remains unclear. Here, we found that SAS-6 assembly can be shaped by preexisting (or mother) centrioles. During S phase, SAS-6 molecules are first recruited to the proximal lumen of the mother centriole, adopting a cartwheel-like organization through interactions with the luminal wall, rather than via their self-oligomerization activity. The removal or release of luminal SAS-6 requires Plk4 and the cartwheel protein STIL. Abolishing either the recruitment or the removal of luminal SAS-6 hinders SAS-6 (or centriole) assembly at the outside wall of mother centrioles. After duplication, the lumen of engaged mother centrioles becomes inaccessible to SAS-6, correlating with a block for reduplication. These results lead to a proposed model that centrioles may duplicate via a template-based process to preserve their geometry and copy number.
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http://dx.doi.org/10.1016/j.devcel.2014.05.008 | DOI Listing |
Mol Biol Cell
January 2025
Dept. of Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198.
The primary cilium is a crucial signaling organelle that can be generated by most human cells, and impediments to primary ciliogenesis lead to a variety of developmental disorders known as ciliopathies. The removal of the capping protein, CP110, from the mother centriole is a crucial early step that promotes generation of the ciliary vesicle and ciliogenesis. Recent studies have demonstrated that CP110 undergoes polyubiquitination and degradation in the proteosome, but the mechanisms of unfolding and removal from the mother centriole remain unknown.
View Article and Find Full Text PDFDev Cell
December 2024
Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany; Cell Biology and Biophysics Unit, EMBL, 69117 Heidelberg, Germany. Electronic address:
Centrosomes organize microtubules that are essential for mitotic divisions in animal cells. They consist of centrioles surrounded by pericentriolar material (PCM). Questions related to mechanisms of centriole assembly, PCM organization, and spindle microtubule formation remain unanswered, partly due to limited availability of molecular-resolution structural data inside cells.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Brain neurons utilize the primary cilium as a privileged compartment to detect and respond to extracellular ligands such as Sonic hedgehog (SHH). However, cilia in cerebellar granule cell (GC) neurons disassemble during differentiation through ultrastructurally unique intermediates, a process we refer to as cilia deconstruction. In addition, mature neurons do not reciliate despite having docked centrioles.
View Article and Find Full Text PDFCell Commun Signal
December 2024
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea.
The primary cilium is a cellular organelle whose assembly and disassembly are closely linked to the cell cycle. The centriole distal appendage (DA) is essential for the early stages of ciliogenesis by anchoring the mother centriole to the cell surface. Despite the identification of over twelve proteins constituting the DA, including CEP83, CEP89, CEP164, FBF1, and SCLT1, their specific functions in ciliary dynamics are not fully understood.
View Article and Find Full Text PDFBiochem Biophys Res Commun
December 2024
Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA; Graduate Program in Genetics and Epigenetics, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA. Electronic address:
The primary cilium is a cellular antenna to orchestrate cell growth and differentiation. Deficient or dysfunctional cilia are frequently linked to skeletal abnormalities. Previous research demonstrated that ciliary proteins regulating axoneme elongation are essential for skeletogenesis.
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