In:
eLife, eLife Sciences Publications, Ltd, Vol. 2 ( 2013-09-17)
Abstract:
Organisms—and individual tissues—grow and develop by dividing their cells. However, the process of cell division does not have to be symmetric, and the fates of the cells can be very different if cellular contents, including RNAs or proteins, are exclusively retained in the ‘mother’ or passed to her ‘daughter’. Organelles known as centrioles can play an important part in influencing whether cell division is symmetric or asymmetric. Centrioles contain ordered assemblies of various proteins, and mutations in some of these proteins can cause developmental defects in humans. For example, mutations in the centriolar proteins CPAP and STIL cause a syndrome known as microcephaly, in which the brain is smaller than normal. Although CPAP and STIL are known to bind each other, how they interact on a molecular level to form centrioles—and how this interaction is disrupted in microcephaly—is not well understood. Cottee et al. have now used structural and biochemical assays to explore how these two proteins bind to each other, and have identified specific amino acid residues that enable this interaction. These residues are highly conserved across many organisms, and a mutation in one of them has previously been associated with microcephaly in humans. Now, Cottee et al. demonstrate that this mutation weakens the interaction between CPAP and STIL in vitro. To explore these processes in vivo, Cottee et al. studied mutant fruit flies in which the interactions between CPAP and STIL were weaker than normal, and found that these mutations prevented the normal formation of centrioles. Furthermore, there was a striking correlation between the ability to form centrioles in fruit flies and the ability of CPAP and STIL to bind each other, based on the structural model and in vitro binding studies. Cumulatively, these findings reinforce the importance of CPAP and STIL in centriole formation, and suggest that one reason for the development of microcephaly may be defects in the proper formation of centrioles.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.01071.001
DOI:
10.7554/eLife.01071.002
DOI:
10.7554/eLife.01071.003
DOI:
10.7554/eLife.01071.004
DOI:
10.7554/eLife.01071.005
DOI:
10.7554/eLife.01071.006
DOI:
10.7554/eLife.01071.007
DOI:
10.7554/eLife.01071.008
DOI:
10.7554/eLife.01071.009
DOI:
10.7554/eLife.01071.010
DOI:
10.7554/eLife.01071.011
DOI:
10.7554/eLife.01071.012
DOI:
10.7554/eLife.01071.013
DOI:
10.7554/eLife.01071.014
DOI:
10.7554/eLife.01071.015
DOI:
10.7554/eLife.01071.016
DOI:
10.7554/eLife.01071.017
DOI:
10.7554/eLife.01071.018
DOI:
10.7554/eLife.01071.019
DOI:
10.7554/eLife.01071.020
DOI:
10.7554/eLife.01071.021
DOI:
10.7554/eLife.01071.022
DOI:
10.7554/eLife.01071.023
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2013
detail.hit.zdb_id:
2687154-3
Permalink