Reports and Publications
·
Grant recipients will be asked
to complete a progress report after six months and interim progress reports will
be requested at the end of each milestone. A lay description must accompany
each report that should be suited to publication on the LST web site.
Dundee Report June 2005
Using powerful electron microscopes we have studied the distribution of the cell protein involved in causing Lowe syndrome, called OCRL1.
We found only a small fraction of OCRL1 in a structure called the Golgi complex, which processes and sorts out newly made membranes (the Golgi complex was considered previously to be a primary site of OCRL1 action). Our study found most of OCRL1 in the membrane that encloses the cell and in structures that process membrane packages that the cell uses to take up substances from its environment (endosomes).
We have also analysed the function of the Lowe protein using novel methods for locating the fat-like lipid substances that might be regulated by the Lowe protein in different cell structures. The lipid types processed by OCRL1 are known to be important for generating vesicle packages, which transport proteins within cells. We find these lipids are strongly regulated by OCRL1 in only a few cell structures inside the cell, especially at the Golgi complex and endosomes.
These studies indicate that OCRL1 has important functions to maintain the balance of lipids inside cells rather than at the cell membrane, and suggest that in cells from boys with Lowe syndrome a disturbed lipid balance at the cell interior could be the key to understanding this disorder.