Flatworms' minimalist approach to cell division reveals molecular architecture of human centrosome

Jan 05, 2012
Centrioles (shown in green) serve as anchor points for cilia (shown in red) -- tiny projections on the surface of cells that help move fluid and mucus around the brain, lung, eye and kidney and propel eggs down fallopian tubes. The freshwater planarian Schmidtea mediterranea use ciliated cells lining its pharynx (shown above) to ingest food. Credit: Image: Courtesy of Dr. Juliette Azimzadeh, University of California, San Francisco

Researchers at the University of California, San Francisco and the Stowers Institute for Medical Research have discovered that planarians, tiny flatworms fabled for their regenerative powers, completely lack centrosomes, cellular structures that organize the network of microtubules that pulls chromosomes apart during cell division.

The flatworms' unique and unexpected characteristic, detailed in the Jan. 5, 2012 issue of , not only allowed lead author Juliette Azimzadeh, Ph.D., to identify a large set of conserved proteins required for centriole assembly in but it also indicates that , long thought to be required primarily for such as , have been retained in other to coordinate specific developmental rather than .

"It came as a surprise to all of us that planarians could get rid of centrosomes without affecting their regenerative potential," says Howard Hughes Medical Institute and Stowers investigator Alejandro Sánchez Alvarado, Ph.D. "It suggests to us that the evolutionary pressure to maintain centrosomes may have very little to do with cell division itself. There may be another function for centrosomes that is still obscured."

Centrosomes are composed of two centrioles, which are arranged perpendicular to each other and are surrounded by an amorphous mass of proteins known as the pericentriolar material. Each centriole consists of nine microtubule triplets that are assembled into a hollow structure resembling a cartwheel. Although the molecular composition of the centrosome has been determined in human and flies, the function of most components is still unclear.

Complicating matters is the fact centrioles pull double duty: In addition to forming the core of centrosomes, they serve as anchor points for cilia—tiny projections on the surface of cells that not only help move fluid and mucus around the brain, lung, eye and kidney and propel eggs down fallopian tubes, but are also essential to sight, smell, mechanosensation and intercellular signaling. Not surprisingly, a number of diseases trace their origins to defects in ciliogenesis.

The freshwater flatworm Schmidtea mediterranea lives in southern Europe and Northern Africa is the first animal ever discovered without a crucial structure inside its cells known as the centrosome. Credit: UCSF/J.Azimzadeh

Flatworms like the freshwater planarian Schmidtea mediterranea use ciliated cells lining their pharynx or underside to keep food or themselves moving. "The fact that centrioles were retained in this organism while centrosomes were lost, really speaks to the idea that centrioles evolved primarily for making cilia, and not for their mitotic functions. " says senior author Wallace Marshall, Ph.D., an associate professor in the Department of Biochemistry & Biophysics at UCSF, who is particularly interested in the function and duplication of centrioles.

To determine which centrosome components are required for the assembly and function of its centriole core, Azimzadeh, a postdoctoral researcher in the lab of Marshall, decided to join forces with Sánchez Alvarado and take advantage of planarians' ease of genetic manipulation.

When she shut down two planarian homologues of genes known to be required for centrosome assembly in other species, she found that the formation of cilia was perturbed. "But surprisingly, these animals had no regeneration defects," says Azimzadeh.

The remarkable ability of planarians to regenerate whole animals from almost any part of their body requires the proliferation of so-called neoblasts, a population of totipotent stem cells and the only cells to undergo cell division. "We thought that when we silenced those genes, cell division would be inhibited and planaria wouldn't be able to regenerate," explains Sánchez Alvarado. "You would expect to see a drop in the number of cells that undergo cell division. But the numbers are fine."

When Azimzadeh scrutinized normal for the presence of centrioles with the help of immunofluorescence and transmission electron microscopy, she couldn't detect centrioles in any other cell type with the exception of ciliated cells. "Our results indicate that planarians don't assemble centrosomes," says Azimzadeh. "The absence of centrioles in dividing cells implies that planarians do not use the pathway for centriole duplication that underlies centrosome reproduction in other animals, but only assemble centrioles de novo during the differentiation of ciliated cells."

Based on this finding, the researchers predicted that proteins specifically required for centrosome duplication and function should have been eliminated from the planarian genome during evolution. An extensive search for planarian homologs for known human centromere components revealed that eight out of 55 centrosome signature proteins that were unequivocally present in the last common ancestor are missing from the planarian genome.

On the flip-side, the researchers hypothesized, components of the human centrosome for which homologs are still present in planarians should be required for either de novo assembly of centrioles or for ciliogenesis. When Azimzadeh systematically knocked down these genes, the majority led to ciliary-based motility defects likely caused by misassembled or malfunctioning centrioles.

"The fact that we could use planarians to identify functions for human genes that didn't have known functions before, really emphasizes the importance of evolutionary and developmental perspectives in addressing cellular mechanisms," says Sánchez Alvarado.

Explore further: Fungus deadly to AIDS patients found to grow on trees

Provided by Stowers Institute for Medical Research

5 /5 (1 vote)

Related Stories

Researchers Uncover Protein's Role In Cell Division

Jun 15, 2010

(PhysOrg.com) -- A Florida State University researcher has identified the important role that a key protein plays in cell division, and that discovery could lead to a greater understanding of stem cells.

Making cells turn cartwheels

Feb 01, 2011

Centrioles are barrel-shaped connection hubs that, like key Meccano parts, hold together the microtubule connection rods that form the structural framework of the cells in our bodies.

'Birth control' for centrioles

Jan 26, 2009

Like DNA, centrioles need to duplicate only once per cell cycle. Rogers et al. uncover a long-sought mechanism that limits centriole copying, showing that it depends on the timely demolition of a protein that ...

DNA 'tattoos' link adult, daughter stem cells in planarians

Sep 10, 2008

Unlike some parents, adult stem cells don't seem to mind when their daughters get a tattoo. In fact, they're willing to pass them along. Using the molecular equivalent of a tattoo on DNA that adult stem cells (ASC) pass to ...

Recommended for you

Some anti-inflammatory drugs affect more than their targets

16 hours ago

Researchers have discovered that three commonly used nonsteroidal anti-inflammatory drugs, or NSAIDs, alter the activity of enzymes within cell membranes. Their finding suggests that, if taken at higher-than-approved ...

Researchers discover new strategy germs use to invade cells

Aug 20, 2014

The hospital germ Pseudomonas aeruginosa wraps itself into the membrane of human cells: A team led by Dr. Thorsten Eierhoff and Junior Professor Dr. Winfried Römer from the Institute of Biology II, members of the Cluster ...

Progress in the fight against harmful fungi

Aug 20, 2014

A group of researchers at the Max F. Perutz Laboratories has created one of the three world's largest gene libraries for the Candida glabrata yeast, which is harmful to humans. Molecular analysis of the Candida ...

How steroid hormones enable plants to grow

Aug 19, 2014

Plants can adapt extremely quickly to changes in their environment. Hormones, chemical messengers that are activated in direct response to light and temperature stimuli help them achieve this. Plant steroid ...

User comments : 0