Inside every cell, thousands of proteins must reach the right place at the right time. Helping coordinate this complex logistics network are centriolar satellites—tiny, membrane-less organelles that play important roles in protein trafficking, cell division, and the formation of cilia.
Despite their importance and their links to developmental and neurological disorders, the molecular mechanisms through which centriolar satellites assemble and acquire their functions have remained poorly understood.
A new study led by Dr. Elif Nur Fırat-Karalar from Koç University’s Department of Molecular Biology and Genetics and School of Medicine reveals that centriolar satellites form through a highly ordered, hierarchical process rather than through the random aggregation of proteins. The findings were published in the Journal of Cell Biology.
PCM1 acts as the organelle’s central scaffold
The researchers found that centriolar satellite formation begins when a protein called pericentriolar material 1, or PCM1, assembles into a scaffold-like structure. This initial scaffold then recruits other centriolar satellite proteins, known as clients, in a defined sequence.
To observe this process, the team developed new cellular and in vitro experimental systems that allowed them to follow centriolar satellite biogenesis over time. These tools revealed distinct stages of assembly, remodeling, and maintenance.
The experiments showed that PCM1 can intrinsically form granules through multimerization—the binding of multiple PCM1 molecules to one another. This process is regulated by the cytoskeleton and by proteins associated with ciliary diseases.
The results indicate that PCM1 serves as the core organizing scaffold upon which centriolar satellites are built.
A sophisticated internal architecture
High-resolution imaging revealed that centriolar satellites are not structurally uniform. PCM1 and the proteins it recruits occupy distinct subdomains within the organelle, each with different compositions and dynamic properties.
This spatial organization suggests that centriolar satellites have a considerably more sophisticated internal architecture than previously recognized. Rather than functioning simply as passive storage sites, they appear to be active organizational hubs that coordinate the positioning, storage, and transport of proteins within the cell.
The researchers also showed that PCM1 alone was sufficient to form an internally organized scaffold, selectively recruit specific proteins, and interact with microtubules, which form part of the cell’s internal transport system.
Why centriolar satellites matter
Centriolar satellites contribute to the formation and function of cilia—microscopic projections often described as the cell’s “antennae.” Cilia enable cells to detect and respond to signals from their surroundings and are essential for the normal functioning of organs including the brain, kidneys, eyes, and skeleton.
Defects in cilia can cause a range of disorders, including vision loss, kidney disease, developmental abnormalities, and neurological conditions. Mutations in PCM1 have also been associated with schizophrenia, while alterations affecting other centriolar satellite proteins have been linked to microcephaly and ciliopathies.
By disrupting PCM1 assembly, the researchers demonstrated that the proper formation of centriolar satellites is important for key cellular signaling pathways and normal cell division.
New tools for studying membrane-less organelles
One of the study’s major contributions is the development of experimental tools that enable scientists to examine centriolar satellite formation step by step.
Studying this process has previously been difficult because centriolar satellites are continuously present in cells and constantly remodel their structures. The cellular and in vitro biogenesis assays developed by the team make it possible to measure how their properties change during assembly and maintenance.
These approaches could also provide a broader framework for investigating other membrane-less organelles—cellular compartments that lack a surrounding membrane but nevertheless assemble into organized structures with specialized functions.
By establishing PCM1 as the central scaffold of centriolar satellites and revealing the hierarchical pathway through which they form, the study provides new insight into the fundamental principles of cellular organization. The findings and experimental tools may ultimately help researchers investigate how disease-associated mutations disrupt cellular architecture and function.
The research was supported by the European Research Council, the Scientific and Technological Research Council of Türkiye (TÜBİTAK), and the Istanbul Development Agency.