Sas 6Edit
SAS-6 is a highly conserved centriolar protein that plays a central role in the duplication of the centriole, a cylindrical cellular organelle essential for organizing the mitotic spindle during cell division. The protein is best known as a core component of the centriole cartwheel, a ninefold-symmetrical scaffold at the proximal end of the organelle that templates the arrangement of microtubule triplets. In this way, SAS-6 helps establish the foundational architecture that allows a daughter centriole to form once per cell cycle, ensuring proper genome segregation and cell viability. Its activity is coordinated with a network of other duplication factors, and it is present across a wide range of eukaryotes, including animals, plants, and fungi. The study of SAS-6 continues to shed light on how cells build complex intracellular structures with remarkable precision.
In humans and many other organisms, SAS-6 exists alongside a family of related proteins and paralogs that can modulate centriolar assembly in nuanced ways. The molecular interactions that recruit SAS-6 to the site of duplication, promote its oligomerization into the cartwheel, and then integrate with downstream components help explain why centrioles are robust yet tightly regulated machines. Disruptions to this system—whether by genetic mutation or misregulation of the cell cycle—can lead to abnormalities in centriole number and structure, with consequences for cell division and tissue development. The study of SAS-6 intersects with broader themes in cell biology, including centrosome biology, spindle formation, and the mechanisms cells use to maintain genome integrity.
Structure and domains
SAS-6 is a dimeric protein that self-assembles into higher-order structures capable of templating a ninefold symmetric scaffold. The protein contains regions that drive dimerization and oligomerization, enabling the formation of the cartwheel ring that seeds centriole assembly. In different species, the precise domain organization can vary, but the conserved ability to form stable coiled-coil–mediated interactions underpins its function. The resulting cartwheel provides a geometric blueprint that orients the peripheral microtubule blades of the centriole, aligning the microtubule triplets in a precise arrangement around the central axis. For a broader view of the assembly process, see the role of the cartwheel cartwheel (centriole) in centriole biogenesis.
SAS-6 is encoded by the gene SAS-6 and is part of a network of centriole-associated proteins. Its structure supports interactions with other core factors that are essential for initiation and progression of centriole duplication.
Assembly of the cartwheel and centriole duplication
During the cell cycle, SAS-6 is recruited to the mother centriole in a regulated sequence that involves multiple signaling inputs. One key regulator is the kinase PLK4, whose activity helps coordinate the timing of SAS-6 recruitment and cartwheel assembly. Once localized, SAS-6 oligomerizes to form the central part of the cartwheel, and this scaffold defines the ninefold symmetry that templates the nascent centriole’s peripheral microtubules. The cartwheel serves as a platform for integrating additional components, such as STIL and CEP135, which contribute to elongation and stabilization of the daughter centriole. As the duplication program proceeds, other factors like CPAP assist in elongation of the centriole while maintaining proper geometry.
In many organisms, the cartwheel is a transient structure that persists during the early stages of centriole assembly and may be remodeled as the centriole matures. The precise choreography among SAS-6, its paralogs, and interacting partners ensures that a single daughter centriole forms per cell cycle and that centriole number remains tightly controlled. Experimental perturbations that reduce SAS-6 function typically block cartwheel formation and centriole duplication, underscoring the essential nature of SAS-6 in this process.
Regulation and interactions
SAS-6 operates within a regulatory network that integrates cell signaling, kinase activity, and structural assembly. Phosphorylation by PLK4, for example, modulates the recruitment and stability of SAS-6 at the site of duplication. Interactions with STIL are particularly important: STIL acts as a recruitment factor and stabilizer, helping to position SAS-6 and promote cartwheel formation. CEP135 (also known as BLD10 in some organisms) cooperates with SAS-6 to connect the cartwheel to the surrounding microtubule framework, contributing to the overall integrity of the daughter centriole.
Other proteins involved in centriole biology interact with SAS-6 or function in parallel pathways to ensure proper duplication and maturation. The balance of synthesis, assembly, and disassembly of centrosomal components is critical to maintaining genome stability during cell division, and SAS-6 sits at a pivotal junction in that balance. In some lineages, paralogs such as SAS6L may participate in related or distinct aspects of centriole-related biology, illustrating the diversification of the centriole assembly toolkit across evolution.
Evolution and diversity
SAS-6 is one of the most highly conserved centriole components across eukaryotes, reflecting its fundamental role in cell biology. The core mechanism of cartwheel-driven centriole duplication appears to be preserved from as diverse species as unicellular organisms to vertebrates, though lineage-specific variations in regulation and accessory factors reflect adaptations to different cellular contexts. Some organisms possess paralogs or related proteins that can modulate cartwheel assembly or function in tissue-specific or developmental contexts, highlighting how the centriole duplication machinery can be tuned without losing its essential core.
The existence of paralogs such as SAS6L demonstrates that cells may reuse or repurpose cartwheel-related modules in new ways, potentially contributing to specialized centrosome architectures or cilia-related structures in certain tissues. Comparative studies across species help clarify which features of SAS-6 are absolutely conserved and which reflect evolutionary flexibility.
Clinical significance
Abnormalities in centriole duplication factors, including SAS-6, have been investigated in relation to human disease and developmental disorders. Defects in centriole biogenesis can contribute to problems with cell division, cilia formation, and tissue development, and researchers study SAS-6 alongside other core centriole proteins to understand these conditions. While most clinical associations are part of a broader picture that includes multiple centrosomal components, continued research into SAS-6 helps illuminate how precise centriole assembly supports healthy development and genome stability.