Screening methods for compounds useful in the treatment of polycystic kidney disease

A method for identifying a compound capable of modulating polycystin-2 mediated increase in apical expression of NaK-ATPase on the cell membrane, comprising:

• (a) contacting a test compound to a cell expressing a polycystin-2 protein wherein expression of said polycystin-2 protein results in an increase in apical expression of NaK-ATPase on the cell membrane;
• (b) measuring apical expression of NaK-ATPase on the cell membrane;
• and
• (c) comparing the level of apical expression of NaK-ATPase on the cell membrane obtained in (b) to the level of apical expression of NaK-ATPase on the cell membrane obtained in the presence of a vehicle control:
• wherein a decrease in the level of apical expression of NaK-ATPase on the cell membrane obtained in (b) compared to that obtained in the presence of a vehicle control, indicates identification of a compound capable of modulating polycystin-2 activity.

A method for identifying a compound capable of modulating polycystin-2 mediated increased expression of β-2-NaK-ATPase , comprising;

• (a) contacting a test compound to a cell expressing a polycystin-2protein wherein expression of said polycystin-2 protein results in an increased expression of β-2-NaK-ATPase within the cell;
• (b) measuring expression of β-2-NaK-ATPase within the cell;
• and
• (c) comparing the level of expression of β-2-NaK-ATPase within the cell obtained in (b) to the level of expression of β-2-NaK-ATPase within the cell obtained in the presence of a vehicle control:
• wherein a decrease in the level of expression of β-2-NaK-ATPase on the cell membrane obtained in (b) as compared to that obtained in the presence of a vehicle control, indicates identification of a compound capable of modulating polycystin-2 activity.

A method for identifying a compound capable of modulating polycystin-2 mediated decreased incorporation of focal adhesion kinase into focal adhesion complexes, comprising;

• (a) contacting a test compound to a cell expressing a polycystin-2 protein wherein expression of said polycystin-2 protein results in a decreased incorporation of focal adhesion kinase into focal adhesion complexes;
• (b) measuring incorporation of focal adhesion kinase into focal adhesion complexes;
• and
• (c) comparing the level of incorporation of focal adhesion kinase into focal adhesion complexes obtained in (b) to the level of incorporation of focal adhesion kinase into focal adhesion complexes obtained in the presence of a vehicle control:
• wherein an increase in the level of level of incorporation of focal adhesion kinase into focal adhesion complexes obtained in (b) as compared to that obtained in the presence of a vehicle control, indicates identification of a compound capable of modulating polycystin-2 activity.