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.
While much interest has been focused on the signaling
pathways connected to mGluR’s, these interactions with
the cytoskeleton may have important implications for
understanding the basic mechanisms of Fragile X. Dr.
Giangrande will investigate these interactions in detail in
fruit flies, which are a simple yet powerful system in which
multiple genes can be manipulated with relative ease.