11 February, 2013

"Functional Amyloid"

"Functional amyloid" is a term I first heard about 3 years ago at the XII Amyloidosis Symposium in Rome. There was an oral presentation about the organization of peptide hormones in the secretory granules of the pituitary. Prior to that, I , like most clinicians, only thought about amyloid in the context of disease. It turns out amyloid actually plays an important role in vertebrate and invertebrate biology. 

In bacteria amyloid fibrils are involved in biofilm formation and cell/cell cell/substrate adhesion. Amyloid comprised of curli proteins in E.coli and Salmonella are a well-described example (see figure). Functional amyloid is also produced by Saccharomyces and Candida

source: http://www.mcdb.lsa.umich.edu/labs/chapman/research.php
The oval-shaped things are bacteria; the mesh-like stuff in between them is curli amyloid. 
As in amyloid diseases, the protein fibrils are extracellular; unlike these conditions, the production of amyloid appears to be a highly regulated process with intracellular trafficking, cellular export, fibril nucleation and the rapid polymerization requiring complex interactions between several curlin subunits (CsgA though G).  Its actually pretty interesting. No really, it is.

source: http://www.sciencedaily.com/releases/2008/02/080215121210.htm
A bacterial biofilm. Credit: Janice Haney Carr in Science Daily
In humans, a type of functional amyloid made up of a protein called pmel17 plays a role in the polymerization of the pigment melanin. Smaller melanin precursors (the building blocks from which melanin is ultimately constructed) would be toxic to the cell if they were not sequestered inside melanosomes by pmel17 amyloid. As defined by freemedicaldictionary.com, melanosomes are cigar- or oval-shaped pigment-containing granules within melanocytes. These granules are injected into keratinocytes, providing color:

source: http://www.katzenzeitung.eu/en/Genetics/melanocytes.html
Thus, pmel17 amyloid is critical for the formation of melanin and also cellular protection during this process. Click here for a link to an article discussing this in detail. 

The presentation in Rome I mentioned at the outset of this post discussed yet another functional role for amyloid in humans. Peptide hormones in the pituitary gland are actually stored as amyloid within secretory granules. It is postulated that this structure permits on the one hand, enduring stability in a highly concentrated state, and on the other, a means of controlled release of the hormones in question. Click here to read a publication from the authors of that presentation. 

There are illnesses characterized by abnormal amyloid or amyloid-like protein aggregates inside cells ("inclusion bodies"). An example would be Lewy Bodies in the neurons of patients with Parkinson's Disease. This type of protein accumulation is not functional amyloid, as it is generally damaging to the cell.

One can hope that understanding how cells handle functional intracellular amyloid will eventually provide insights into the pathophysiology of these disease states and perhaps lead to effective treatments. 

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