Drosophila CYFIP, a Molecular Link Between Actin Cytoskeleton Remodeling and Fragile X

With funding from FRAXA Research Foundation from 2004-2006, Dr. Angela Giangrande at the Universite Louis Pasteur investigated the interactions between dendrites, messenger mRNA, and the cytoskeleton in fruit flies, which are a simple yet powerful system in which multiple genes can be manipulated with relative ease.

Angela Giangrande, PhD, Universite Louis Pasteur, FRAXA research grant
$130,000 Grant
Angela Giangrande, PhD
Principal Investigator
Universite Louis Pasteur
2004-2006 FRAXA Research Grant
$130,000 over 3 Years

Drosophila CYFIP, a Molecular Link Between Actin Cytoskeleton Remodeling and Fragile X Project Plan

by Angela Giangrande, 1/1/2004

The normal function of FMRP, the protein missing in Fragile X, involves two primary actions:

1. regulation of protein synthesis in dendrites, and

2. transport of messenger RNA from the nucleus of the cell to the dendrites.

Both these functions require significant interactions with the cytoskeleton, the scaffold which holds the cell together. In the first instance, cytoskeletal changes (dendritic spines become long and thin) occur whenever LTD (Long Term Depression) occurs, and this is known to occur too much in Fragile X. In the second case, transport of mRNA requires that FMRP hook onto the cytoskeleton and propel itself along, like a railroad train, to transport the mRNA to the dendrite, where it will be used as the template for protein synthesis. Clearly, these two functions are closely related, and both appear to be stimulated by activation of metabotropic glutamate receptors.

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