NSF, Unc-18-1, dynamin-1 and HSP90 are inclusion body components in neuronal intranuclear inclusion disease identified by anti-SUMO-1-immunocapture

© Springer-Verlag 2008Neuronal intranuclear inclusion disease, a progressive ataxia that may be familial or sporadic, is characterized by numerous neuronal intranuclear inclusion bodies similar to those found in polyglutamine repeat diseases. Previously, we found that the intranuclear inclusion bodies are intensely immunopositive for SUMO-1, a protein which covalently conjugates to other proteins in a similar way to ubiquitin. To identify the SUMO-1-associated proteins in the inclusion bodies, we isolated intranuclear inclusion bodies from fresh, frozen brain tissue of a case with familial neuronal intranuclear inclusion disease and solubilized the proteins. SUMO-1-associated inclusion body proteins were then immunocaptured using an anti-SUMO-1 antibody. The proteins, NSF, dynamin-1 and Unc-18-1 (rbSEC1), involved in membrane trafficking of proteins, and the chaperone HSP90, were identified following anti-SUMO-1-immunocapture by using tandem mass spectrometry and database searching. Immunohistochemistry of brain sections and crude brain homogenates of three cases of familial neuronal intranuclear inclusion disease confirmed the presence of these proteins in intranuclear inclusions.Dean L. Pountney, Mark J. Raftery, Fariba Chegini, Peter C. Blumbergs, Wei Ping Ga

Potassium leak channels and the KCNK family of two-P-domain subunits

With a bang, a new family of potassium channels has exploded into view. Although KCNK channels were discovered only five years ago, they already outnumber other channel types. KCNK channels are easy to identify because of their unique structure - they possess two pore-forming domains in each subunit. The new channels function in a most remarkable fashion: they are highly regulated, potassium-selective leak channels. Although leak currents are fundamental to the function of nerves and muscles, the molecular basis for this type of conductance had been a mystery. Here we review the discovery of KCNK channels, what has been learned about them and what lies ahead. Even though two-P-domain channels are widespread and essential, they were hidden from sight in plain view - our most basic questions remain to be answered