Saturday, February 23, 2013

DISTURBANCES IN THE DIFFERENTIATION:
THE CASE OF AUTOSOMAL POLYCYSTIC KIDNEY DISEASE.

This disease is a clear example of differentiation gone rogue.  In the Collecting tubule of kidney, the cells have ciliary bodies which have censors to feel reportedly general urine direction and help incidentally things along.
At Molecular level these Ciliary bodies have a skeleton and a large extracellular protein which is transmembrane, meaning it crosses the cellular membrane to impact calcium Homeostasis inside the cell.  This Molecule/protein is made by the PDK-1 gene.  This gene is located on Chromosome 16.
Through splicing error or mutation in this gene, This Ciliary body goes missing.
2 things happen then:

1:  The cell dies and details are lost this point
we know that even at the peri-membrane level Caspases can be triggered.  After all the Caspase are in the Cytosol.   However at the time of the 2nd hit event, the cell is stressed and through the MAPK pathway, the c-Jun can be stimulated also.  Whatever the case these cells can be destroyed.

2.The other path follows gene interactions.
We know that PDK-1 interact with RSG7 which in turn interact with SNAPAP ( a BLOC-1 component)
RSG7 is a Regulator of G-protein Signaling 7.  acting somewhat as a promoter gene for SNAPAP sitting on BLOC1,   And BLOC-1 is important in the formation of specialized organelles in the endosomal-lysozomal systems (Melanosome, and Platelet dense granules).  This where differentiation is involved in the activity of BLOC-1.   If differentiation is our Target, disabling BLOC-1 is it.  This is a large molecule with many importatnt components, it is an intersection of roads in the cell!

Continuing our story, BLOC-1 will interact with Dysbindin and Pallidin, 2 very interesting Molecules in this disease.  Pallidin deals with intracellular vesicle  trafficking, and through its interaction with syntaxin 13, it has impact of membrane fusion and division.   This bring the notion of Vacuolization which could explain also Cystic formation (speculation that needs proof of concept).  But you see where I am coming from.

The Dysbindin is very important here, the skeleton of the ciliary body could come from activity in this protein but remember that the skeleton of the cell is also its nervous system.  Some forms of Schizophrenia is linked to disturbances in the Dysbindin.  Indeed you will find the individual suffering from this disease with a certain odd personality... mostly with obsessive and stubborn tendencies in my experience.

Individual with this diagnosis should be on ACE inhibitor, or the new TOLVAPTAN!
and should never have Caffeine which promotes the growth of cysts.

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