Saturday 3 June 2006
GDP dissociation inhibitors (GDIs) are proteins that regulate the GDP-GTP exchange reaction of members of the rab family (RABS), small GTP-binding proteins of the ras superfamily, that are involved in vesicular trafficking of molecules between cellular organelles.
The rab proteins (RABs) undergo activation upon GTP binding, and GTP hydrolysis to GDP inactivates the protein. GDIs slow the rate of dissociation of GDP from rab proteins and release GDP from membrane-bound RABs.
X-linked nonspecific mental retardation
The genetic background of X-linked nonspecific mental retardation is very heterogeneous, with at least 50 loci thought to be involved in different families.
In a subgroup of families with this disorder, the genetic defect is in the gene encoding the Rab guanosine diphosphate (GDP)-dissociation inhibitor, a protein that controls the intracellular recycling of Rab GTPases.
These proteins can bind GDP-bound Rab proteins and deliver them in a controlled manner to specific organelles.
This situation resembles that in choroideremia, in that the GDP-dissociation inhibitors constitute a family of protein isoforms, of which the isoform is predominantly expressed in the central nervous system.
Mutant GDP-dissociation inhibitor may not be able to recycle Rab proteins efficiently in vivo.
Thus, mutations in GDP-dissociation inhibitors may ultimately alter synaptic transmission.
Furthermore, studies in mice suggest that GDP-dissociation inhibitor has a role in neuronal differentiation.
The surprisingly mild phenotypic effects of mutations of GDP-dissociation inhibitor are probably due to the presence of other, "housekeeping" isoforms of these proteins in neurons.
GDI1 germline mutations in X-linked nonspecific mental retardation linked to Xq28 MRX41 and MRX48
- They can be considered as defects in the machinery for the docking and fusion of transport vesicles
X-linked mental retardation (MRXs)