Targeting of the Phosphoinositide

Targeting of the Phosphoinositide Phosphatase OCRL1 to the Golgi Apparatus by Martin Lowe

What we have found is that OCRL1 is present on a membrane compartment in the cell called the early endosome. This is a place that receives material taken up from the cell surface (eg hormones, nutrients, and in the proximal tubule proteins bound to a receptor called megalin). It also receives newly made proteins bound to other receptors from another compartment called the Golgi apparatus. The endosome sorts these various molecules and delivers them either back to the cell surface for another round of uptake  (eg megalin)  to the Golgi to pick up more newly synthesised proteins, or to the another compartment where proteins are degraded into amino acids for use by the cell (the lysosome). Proper endosomal function is required for a host of fundamental processes including hormone signalling, cell growth, cell movement, cell-cell interactions, and in the proximal tubule re-absorption of proteins from the urine.

We have found that OCRL is involved in the recycling of receptors from the endosome back to the Golgi. Defects in OCRL1 would therefore be expected to interfere with the retrieval of these receptors  from the endosome to the Golgi, which in turn would affect protein delivery to the endosome. The localisation of OCRL1 to endosomes also raises the possibility of other trafficking defects at the endosome, of which the potentially most interesting is that of megalin in the proximal tubule. We believe  that megalin recycling may be deficient in cells lacking OCRL1 function, and are soon to start studying whether this is indeed the case.

Dr Martin Lowe
School of Biological Sciences
University of Manchester
The Michael Smith Building
Oxford Road, Manchester M13 9PT , UK

Latest papers:

Lowe Syndrome Protein OCRL1 Interacts with Clathrin and Regulates Protein Trafficking between Endosomes and the Trans-Golgi Network: http://www.molbiolcell.org/cgi/content/abstract/E05-02-0120v1

Structure and Function of the Lowe Syndrome Protein OCRL1: http://www.blackwell-synergy.com/doi/abs/10.1111/j.1600-0854.2005.00311.x