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Polycystin-2--an intracellular or plasma membrane channel?

The intracellular location of polycystin-2 is a hotly debated topic in the field of polycystic kidney disease. Two not necessarily mutually exclusive hypotheses state that polycystin-2 is located in the endoplasmic reticulum or in the plasma membrane, respectively. Although a variety of techniques have been employed to prove one or the other location, no definite consensus has been reached yet. It is generally acknowledged, however, that the COOH-terminus of polycystin-2 contains a retention signal for the endoplasmic reticulum. Another facet has been added to the discussion due to the fact that many genes mutated in patients with cystic kidney diseases, among them PKD2, encode proteins which have been detected in primary cilia. Since there is no evidence that the endoplasmic reticulum extends into the primary cilium, polycystin-2 has to reach the plasma membrane at least in this case. An unbiased approach towards elucidating the physiological location of polycystin-2 would involve the characterization of its intracellular trafficking. Using the COOH-terminus of polycystin-2 in a two-hybrid screen, my group has identified a novel coiled-coil protein which we call PIGEA-14 (polycystin-2 interactor, Golgi- and endoplasmic reticulum-associated protein with a molecular weight of 14 kDa). PIGEA-14 also interacts with GM130, a protein associated with the Golgi matrix, and may therefore represent one important component of the trafficking machinery for polycystin-2.[1]

References

  1. Polycystin-2--an intracellular or plasma membrane channel? Witzgall, R. Naunyn Schmiedebergs Arch. Pharmacol. (2005) [Pubmed]
 
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