What is Dr. Zubair Khalid's research focus?

Dr. Zubair Khalid specializes in molecular virology, mRNA vaccine development, and computational biology, with a focus on avian pathogens like IBDV and Avian Reovirus.

Where is Dr. Zubair Khalid currently working?

Dr. Zubair Khalid is a Postdoctoral Research Associate at the University of Maryland (UMD), specifically within the Department of Animal and Avian Sciences.

Centriole Function: Roles in Cell Division

By Dr. Zubair Khalid, DVM, MS, PhD · 2026-09-19

A centriole is a barrel-shaped organelle built from nine microtubule triplets arranged in a ring, and it serves as the core structural element that organizes the centrosome and templates cilia and flagella. Its most direct role in cell division is to act as the seed that builds the centrosome, the primary microtubule-organizing center (MTOC) of most animal cells, and to help position the mitotic spindle poles so chromosomes segregate accurately.

Centriole function matters because the organelle sits at the intersection of three processes that keep cells alive and tissues organized: chromosome segregation, signaling, and cilia formation. When centriole duplication runs once per cell cycle, division is clean. When it runs zero times, extra times, or at the wrong moment, the result is aneuploidy, failed cilia, or developmental disease. The clinical list is short but serious: primary microcephaly, ciliopathies, and cancer.

What a Centriole Actually Is

The term "centriole" is often used loosely, so it helps to fix the definition. A single centriole is a cylinder roughly 0.2 micrometers in diameter and 0.4 micrometers long in a typical mammalian cell, composed of nine microtubule triplets with no central pair. That "9+0" arrangement distinguishes it from the axoneme of a motile cilium, which is "9+2" with a central pair of singlet microtubules.

The cylinder has two ends that do different jobs. The proximal end carries the cartwheel, a ninefold-symmetric scaffold built around the protein SAS-6 (spindle assembly abnormal protein 6). The distal end carries appendages that dock cilia and anchor microtubules. Structural work on the exceptionally long centriole of the protist Trichonympha resolved the cartwheel at high resolution and showed stacked rings of V-shaped SAS-6 tetramers with a 16-nanometer axial periodicity, with the N-terminal head domains of SAS-6 adopting a zigzag stacking pattern [1]. That geometry is what imposes ninefold symmetry on the whole organelle.

The cartwheel and the assembly sequence

Cartwheel assembly is the first step in making a new centriole. The sequence runs in a defined order:

PLK4 (polo-like kinase 4) marks the site on the mother centriole where a daughter will form.
STIL (SCL/TAL1 interrupting locus) is recruited and phosphorylated by PLK4.
SAS-6 is loaded and self-assembles into the cartwheel hub, establishing ninefold symmetry.
CPAP and CEP135 join and drive microtubule triplet elongation.
The cartwheel is later removed as the centriole matures.

This order is not decorative. Work in Drosophila shows that the Ana1/Cep295 protein must be organized correctly for radial expansion of the centriole, and that elongation of the triplet-containing centrioles of primary spermatocytes has different structural demands than radial expansion does [2]. In other words, building the barrel and widening the barrel are separable steps with separable protein requirements.

The A-C linker and centriole integrity

Adjacent microtubule triplets in the proximal region are connected by the A-C linker. Two recently identified A-C linker proteins, CCDC77 and WDR67, plus MIIP, form a complex that sits between triplets [3]. Removing these proteins breaks triplet cohesion and causes the proximal end to fracture. The same study found an unexpected second job for the A-C linker in centriole duplication, acting through regulation of the torus, the ring-shaped protein assembly at the proximal end [3]. Structural integrity and duplication competence are therefore coupled through the same physical module.

A separate proximal structure, the CEP57-CEP63-CEP152 torus, must be recruited early for normal duplication. The microtubule-associated protein NuSAP stabilizes centriole tubulin and is required for the initial loading of CEP57 at the proximal end of the procentriole, which supports a two-step model of torus assembly [4]. Loss of NuSAP causes premature centriole disengagement and disrupts pericentriolar material cohesion.

Centriole Versus Centrosome Versus Basal Body

This is the comparison students get wrong most often. A centriole is one barrel. A centrosome is two centrioles (one mother, one daughter) plus a cloud of pericentriolar material (PCM). A basal body is a centriole that has docked at the membrane and started templating a cilium.

Feature	Centriole	Centrosome	Basal Body
Composition	Nine microtubule triplets, cartwheel at proximal end	Two centrioles plus pericentriolar material	One mature centriole with distal and subdistal appendages
Core function	Templates the centrosome and the cilium	Primary microtubule-organizing center of proliferating cells	Nucleates and anchors a cilium or flagellum
Microtubule nucleation	Low on its own	High, through gamma-tubulin ring complexes in the PCM	Nucleates the axoneme, not a spindle
Number per cell	Two in G1, four after S phase	One in G1, two after S phase	Dozens to hundreds in multiciliated cells
Cell cycle behavior	Duplicates once per cycle, semi-conservatively	Duplicates once per cycle with its centrioles	Forms when a centriole docks at the membrane
Typical cell type	Most animal cells	Most proliferating animal cells	Ciliated and flagellated cells

The PCM is what turns a passive pair of barrels into a nucleation machine. It concentrates gamma-tubulin and other nucleating factors, and it is the PCM, not the centriole barrel itself, that nucleates the bulk of spindle microtubules [5]. The centriole's contribution is organizational: it recruits and positions the PCM.

The Centriole Duplication Cycle

Centriole duplication is semi-conservative. Each pre-existing centriole produces exactly one daughter per cell cycle, so the mother barrel is retained and a new barrel is built alongside it. The cycle is coordinated with the chromosome cycle at every stage [6].

G1 licensing

In G1, the two centrioles inherited from the previous division are disengaged but remain paired. Licensing makes the mother centriole competent to seed a daughter, and PLK4 abundance is kept low so that no extra seeds form. PLK4 levels are controlled by at least two complementary ubiquitin ligase pathways. The SCF-Slimb/beta-TrCP pathway targets PLK4 based on its phosphorylation state, while CRL4-DCAF1 binds the conserved polo-box 1 and polo-box 2 domains of PLK4 and ubiquitylates it in G2, independent of PLK4 kinase activity, to prevent premature duplication in mitosis [7]. Two ligases reading different features of the same protein is a robust way to keep one seed per mother.

S phase duplication

Duplication happens in S phase, in parallel with DNA replication. PLK4 phosphorylates STIL, STIL recruits SAS-6, and the cartwheel nucleates the daughter barrel. The daughter grows at a right angle to the mother, which is why electron micrographs of S phase cells show orthogonal centriole pairs.

Because the same kinase drives both DNA synthesis timing and centriole duplication timing, the two cycles stay roughly in step. Extra stabilization of the STIL-SAS6 axis is dangerous. Depletion of the E3 ligase FBXW7 causes premature centriole duplication by stabilizing STIL and SAS6, and cancer cell line data show a negative correlation between FBXW7 expression and aneuploidy [8]. The same phosphorylation that lets PLK4 build a new centriole also promotes FBXW7 binding and degradation of the STIL-SAS6 complex, an opposing mechanism that caps duplication [8].

G2 separation and maturation

In G2, the daughter centriole elongates and acquires its full triplet complement. The two centrioles in each pair separate slightly, a step called disengagement, which is a prerequisite for the next round of duplication. The mother centriole also gains distal and subdistal appendages, which are needed for ciliary docking and for focused microtubule organization.

Appendage assembly is a protein network, not a single structure. NDE1 forms a ring at the subdistal appendages, sitting between a more centriole-proximal CEP128 layer and a more peripheral ninein layer. Depleting ODF2 or CEP128 reduces centrosomal NDE1, and NDE1 loss compromises centrosome integrity, reduces centrosomal enrichment of core centriolar proteins, increases separation between paired centrioles, and generates ectopic foci containing multiple centriolar markers [9].

Mitotic spindle pole formation

At mitotic entry, the two centrosomes separate and move to opposite sides of the nucleus, each becoming a spindle pole. The PCM expands dramatically, a process called centrosome maturation, and nucleates the astral and kinetochore microtubules that build the bipolar spindle.

Here the field's language needs care. Centrosomes are the canonical MTOCs of most mammalian cells, but they are not absolutely required for a bipolar spindle. Mouse spermatocytes in which centriole duplication was blocked by Sas4 conditional knockout still progressed through meiosis I and II, segregating chromosomes through a non-centrosomal MTOC [10]. Those non-centrosomal MTOCs used a distinct protein set, including TPX2, KIF11, NuMA, and CAMSAP1-3, which differs from the acentriolar pathway used by oocytes that depends on gamma-tubulin and CEP192 [11]. So the accurate statement is that centrioles organize the dominant spindle-assembly pathway in most animal cells, while backup pathways exist and can carry a division to completion when centrioles are missing.

The flow of the cycle is straightforward to trace.

flowchart TD
    A[G1 licensing] --> B[PLK4 marks the mother centriole]
    B --> C[S phase duplication]
    C --> D[STIL and SAS6 build the cartwheel]
    D --> E[Triplet elongation and A C linker assembly]
    E --> F[G2 disengagement]
    F --> G[Appendage maturation]
    G --> H[Centrosome maturation at mitotic entry]
    H --> I[Bipolar spindle assembly]
    I --> J[Chromosome segregation]
    J --> K[Cytokinesis and one centriole per daughter cell]

How Centriole Function Is Studied

Centriole biology is unusually dependent on imaging, because the organelle is below the diffraction limit of conventional light microscopy. Several approaches are standard.

Ultrastructure expansion microscopy physically expands the sample so that centriolar substructures, including the A-C linker, become resolvable with ordinary optics [3]. STED and structured illumination microscopy resolve ring-like protein distributions at appendages, which is how NDE1 was placed between the CEP128 and ninein layers [9]. Cryoelectron tomography with subtomogram averaging resolves the cartwheel at near-atomic detail without fixation artifacts, which is how the zigzag SAS-6 stacking pattern was defined [1].

Genetic and pharmacological tools complement imaging. Conditional knockout of Sas4 removes centriole duplication in a chosen tissue [10]. Chemical inhibition of PLK4 blocks duplication acutely [11]. The centriole stability assay in Drosophila cultured cells decouples centrosome biogenesis from maintenance, which lets researchers ask what keeps a mature centriole intact rather than what builds it [5]. This distinction matters because centrioles are normally extremely stable, resisting cold treatment and microtubule-depolymerizing drugs that disassemble cytoplasmic microtubules, and the substructures responsible for that stability (microtubule walls, cartwheel, inner scaffold, PCM) are now being mapped [12].

Centriole Function Beyond Division

Cilia and flagella

A mature mother centriole docks at the plasma membrane and becomes a basal body, templating the axoneme of a primary cilium or a motile cilium. In multiciliated cells, this process is amplified dramatically. Multiciliated cell differentiation runs a variant cell cycle that superposes two rounds of centriole biogenesis within a single cycle iteration, producing dozens of mature centrioles that migrate apically and nucleate motile cilia without any cell division [13]. The authors suggest that splitting centriole biogenesis over two cycle iterations in dividing cells may have evolved to allow growth of a solitary primary cilium [13].

Spermatogenesis

Male germ cells handle centrioles differently from female germ cells. Oocytes eliminate centrioles, while spermatocytes retain them through meiosis and pass them to spermatids, where they become basal bodies for the flagellum [14]. Spermatocytes duplicate their centrioles twice, once in early meiotic prophase I and once during interkinesis, and spermatid centrioles then attach to the nucleus and undergo a unique remodeling process [14]. Even when centriole duplication fails, meiosis can complete, but spermatids that inherit fewer than two centrioles show severe defects in spermiogenesis, including improper manchette formation, constricted perinuclear rings, disrupted acrosome morphology, and failure to form flagella, leaving the animal infertile [10].

Signaling and cell cycle control

Centrosomes are activation sites for cyclin/CDK complexes and other cell cycle regulators, which positions them as signaling hubs as well as mechanical organizers [15]. In the ciliate Tetrahymena thermophila, basal bodies are the site of CDK localization, linking cell size to basal body number [15]. Centriolar proteins also feed back into autophagy and proliferation control. A genome-wide screen found that downregulating Wnt, Hippo, Trp53, PIDDosome, ciliary biogenesis, or autophagy pathways allows mouse embryonic stem cells with PLK4-driven centrosome amplification to keep proliferating, and that ARHGAP15 depletion reduces centrosome number through an ATG16L1-dependent autophagy route opposed by ARHGEF2, which is activated by the centriolar protein CEP170 [16]. The centriole is thus wired into stress and growth signaling, not just into mechanics.

When Centrioles Go Wrong: Disease Links

Primary microcephaly

Primary microcephaly is a developmental disorder in which the brain is markedly small at birth. Many of the genes mutated in this condition encode centriolar and centrosomal proteins, including PLK4, STIL, SAS-6, CPAP, and CEP152. The logic is that neural progenitors divide asymmetrically and depend heavily on accurate spindle positioning to balance self-renewal against differentiation. When centriole duplication or PCM recruitment is impaired, spindle orientation drifts, the progenitor pool is depleted prematurely, and the cerebral cortex ends up small. Dysregulation of centriole duplication is directly implicated in developmental disorders of this class [6].

Ciliopathies

Ciliopathies are a family of disorders caused by defective cilia, and because centrioles become basal bodies, mutations in centriole proteins can produce them. The C. elegans protein SAS-1 is homologous to the human ciliopathy component C2CD3. SAS-1 is dispensable for the onset of centriole assembly but essential for organelle integrity during oogenesis, spermatogenesis, and in the early embryo, and it also localizes to the transition zone of sensory neurons and contributes to ciliary function [17]. SAS-1 is required for localizing SSNA-1 to centrioles during oogenesis and to the transition zone during ciliogenesis, and it can recruit SSNA-1 to microtubules in human cells [17]. SSNA-1 itself self-assembles into an antiparallel coiled-coil with a triple-stranded helical junction that forms the microtubule-binding region, and its deletion reduces embryonic viability and causes multipolar spindles [18]. The chain from centriole structural protein to ciliary function to organismal viability is direct.

Cancer

Centrosome amplification, meaning more than two centrosomes per cell, is a long-recognized feature of cancer cells and was first observed as multipolar mitotic spindles in the late nineteenth century [16]. Extra centrosomes can produce multipolar divisions that missegregate chromosomes, and they correlate with chromosomal instability and aneuploidy [6]. Because duplication depends on PLK4, and PLK4 abundance is controlled by multiple degradation pathways, any lesion that stabilizes PLK4 or its downstream partners tilts cells toward amplification [7][8]. The FBXW7-STIL-SAS6 axis is one such node, and its dysregulation links directly to aneuploidy in cancer cell lines [8]. This makes the duplication machinery an active therapeutic target rather than a passive marker [6].

Common Mistakes and Limitations

Treating centriole and centrosome as synonyms. A centrosome contains two centrioles plus PCM. Saying "the centriole nucleates the spindle" skips the PCM, which does most of the nucleation.

Assuming centrioles are universally required for division. They are not. Mouse spermatocytes without centriole duplication complete meiosis using a non-centrosomal MTOC [10], and oocytes use an acentriolar pathway that depends on gamma-tubulin and CEP192 [11]. Centrioles are the dominant organizer in most animal cells, not an absolute requirement.

Forgetting that some organisms and cell types lack centrioles. Plant cells lack centrioles and build spindles without them. Oocytes eliminate centrioles [14]. Differentiated epithelial cells, muscle cells, and neurons can inactivate or lose centrosomes [5]. Any statement about centriole function has to specify the cell type.

Confusing duplication with division. Centriole duplication is a semi-conservative copying event in S phase. Centriole separation and spindle pole formation are later, mechanically distinct events. Blocking duplication does not automatically block chromosome segregation [10].

Over-reading centrosome amplification as a cause of cancer. Amplification is strongly associated with chromosomal instability, but association is not the same as proven causation in every tumor. The mechanistic evidence is strongest for the PLK4, STIL, and SAS-6 axis [7][8].

Assuming centrioles are permanent. They are remarkably stable, but regulated elimination occurs in multiple tissues and organisms, and the substructures that confer stability are only now being defined [12].

Quick Review

A centriole is nine microtubule triplets in a 9+0 barrel, with a SAS-6 cartwheel at the proximal end.
A centrosome is two centrioles plus pericentriolar material, and the PCM does most microtubule nucleation.
Duplication is semi-conservative and once per cell cycle: G1 licensing, S phase duplication, G2 disengagement and maturation, then spindle pole formation.
PLK4 is the master kinase, and its levels are held in check by SCF-beta-TrCP and CRL4-DCAF1 [7].
A centriole becomes a basal body when it docks at the membrane to template a cilium or flagellum.
Centrioles are dispensable for some divisions, including mouse meiosis, because non-centrosomal MTOCs exist [10].
Defects map to primary microcephaly, ciliopathies, and cancer through centrosome amplification and aneuploidy [6][17][8].

Frequently Asked Questions

What is the main function of a centriole?

The main function of a centriole is to seed and organize the centrosome, which is the primary microtubule-organizing center of most animal cells, and to template cilia and flagella when it matures into a basal body.

How is a centriole different from a centrosome?

A centriole is a single barrel of nine microtubule triplets, while a centrosome is a pair of centrioles surrounded by pericentriolar material, which is the structure that actually nucleates most spindle microtubules.

How many times does a centriole duplicate per cell cycle?

Once. Duplication is semi-conservative, so each mother centriole produces exactly one daughter during S phase, and licensing and PLK4 degradation pathways prevent a second round in the same cycle [7].

Do all cells need centrioles to divide?

No. Plant cells lack centrioles entirely, oocytes use an acentriolar pathway, and mouse spermatocytes can complete meiosis using a non-centrosomal MTOC when centriole duplication fails [11][10].

What happens if centriole duplication goes wrong?

Too few centrioles cause ciliary and flagellar defects and contribute to developmental disorders such as primary microcephaly, while too many cause centrosome amplification, multipolar spindles, chromosomal instability, and aneuploidy linked to cancer [6][8].

Are centrioles involved in cell signaling?

Yes. Centrosomes act as activation sites for cyclin/CDK complexes and other cell cycle regulators [15], and centriolar proteins such as CEP170 feed into autophagy and proliferation signaling through the ARHGAP15 and ARHGEF2 axis [16].