Thursday, 17 November 2011

Evolution of NaK-ATPase and ENaC: Part III: ENaC/Degenerin in Naegleria, a protozoa


Naegleria gruberi is a protozoan. Its genome has been sequenced in 2010. This micro-organism has the ability to shift between an amoeba form and a flagellate form. It belongs to the Bikonta branch (two flagella) of Eukaryote, whereas we belong to the Unikonta branch (our spermatozoids have only one flagella). So the common ancestor between Naegleria and animals is directly the last common ancestor of all eukaryotes.

Naegleria gruberi - amoeba-flagellate transformation (MicrobiologyBytes Video Library: http://microbiologybytes.com/video)

Why I am speaking about Naegleria? Because we have found ENaC/Degenerin homologs in the Naegleria gruberi genome. The identity is very low, but some indices plead in favour of true homology (see picture below). For example, the two membrane segments are present and two cysteines are highly conserved. In human, if one of these two cysteines is mutated, the cysteine bridge is broken and leads to the the pseudohypoaldosteronism type 1 syndrome (PHA-1). This important cysteine bridge seems also conserved in Naegleria structure (in yellow, in the centre).
Structural mapping of conserved segments
The structure of the ASIC chicken is represented in two orientations. Transmembrane regions are indicated by lines. In purple are regions well conserved between metazoan and Naegleria sequences. In yellow is the ultra-conserved disulfide bridge involved in the PHA-1 syndrome.

Three interesting points that need further analyses:
  1. Two different scenarii are suggested for the evolution of ENaC/Degenerin:
    1.  ENaC/Degenerin emerged in the Last Common Ancestor of all eukaryotes. And was successively lost in all branches except Naegleria and Animals.
    2. ENaC/Degenerin emerged in the Urmetazoan (the ancestor of Animals) or in the Naegleria ancestor and was horizontally transferred at this stage to the other branch. Horizontal transfers are frequent in Bacteria, but exist also in Eukaryotes, especillay in Naegleria.
  1. The ENaC/Degenerin channel is responsible for sodium sensing in Flies. The transformation of Nagleria amibe to a flagellate form is sensitive to salt concentration changes. Does the EnaC/Degenerin channel responsible for this sensing?
  2. Naegleria gruberi is a tiny and nice organism. Not like his cousin, Naegleria flowerii, who is responsible for brain damages (primary amoebic meningoencephalitis) with a mortality rate of 98% (see animated video here). It is found in 70% of lakes in USA. However, this disease is rare (200 deaths in 2007, compared to the 781'000 due to the Malaria in 2009). There is a need for potential drug targets against this microbe. A recent paper present some of them. The ENaC/Degenerin channel can be blocked by amiloride in Vertebrates. It would be interesting to know if amiloride could also act as a blocker in Naegleria flowerii.

This is the end of my story. I hope you enjoyed this trip at the interface of physiology and evolution. All the details are available in the article.

RAS

Studer, R.A., Person, E., Robinson-Rechavi, M., & Rossier, B.C. (2011). Evolution of the epithelial sodium channel and the sodium pump as limiting factors of aldosterone action on sodium transport Physiological Genomics, 43 (13), 844-854 DOI: 10.1152/physiolgenomics.00002.2011

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