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Fate in fly sensory organ precursor cells could explain human immune disorder
Date:6/21/2009

come the shaft and socket cells on the exterior of the fly's external sensory organ. The pIIb, through two divisions, become the neuron and sheath internal cells of the external sensory organ. These four types of cells become the sensory cluster.

When a cluster of neurons is observed, cell fate determination has gone wrong as too many cells of one kind are being made from the mother cell. Akhila and An-chi found that mutations in the Actin-related protein 3 (Arp3), a component of the seven protein Arp2/3 complex, resulted in the loss of Notch signaling.

This occurs because the ligand Delta a protein that activates the Notch pathway cannot travel properly within the sensory organ cells in the absence of Arp3 protein. In addition, they found that under normal conditions vesicles (tiny bubbles) containing the Notch activating protein Delta travel to the top of the daughter cell to a structure rich in actin. This specialized actin structure contains many membrane protrusions that increase the surface area of cells called microvilli. Under normal circumstances Delta containing vesicles traffic to the microvilli. In the Arp3 mutants, there are significantly fewer microvilli but, more important, the transport of Delta is compromised in Arp3 mutants, affecting the ability of Delta to activate Notch. This is an important part of their work.

"Normally, Delta is presented at the top of the actin structure," said Bellen. It is then encapsulated in the vesicles and travels to the basal, or bottom, of the structure. Delta then travels back to the top of the daughter cells.

Bellen and colleagues have found that the Arp2/3 complex and its activator WASp (Wiskott-Aldrich syndrome protein) function in these daughter cells to transport Delta vesicles to the apical region of the daughter cells. If this complicated trafficking of Delta does not occur, the ability of Delta to activate Notch is compromised.

"It is likely that whatever we
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Contact: Glenna Picton
picton@bcm.edu
713-798-4710
Baylor College of Medicine
Source:Eurekalert

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