Spyryx researches the roles of ENaC and SPLUNC1 in CF while seeking a cure

ENaC is the scientific notation for Epithelial Sodium Channel. The Na refers to natrium, a synonym for sodium. Sodium is the major positive ion in fluid outside of cells. The chemical notation for sodium is Na+.

ENaC is located in the apical membrane of polarized epithelial cells in particular in the kidney (primarily in the distal tubule), the lung, and the colon. In reference to Cystic Fibrosis, ENaC interaction with Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is of important pathophysiological relevance.

CFTR is responsible for chloride transport and defects in this protein cause cystic fibrosis, partly through upregulation of the ENaC channel in the absence of functional CFTR.

In the airways, CFTR allows for the secretion of chloride, and sodium ions and water follow passively. However, in the absence of functional CFTR, the ENaC channel is upregulated, and further decreases salt and water secretion by reabsorbing sodium ions. As such, the respiratory complications in cystic fibrosis are not solely caused by the lack of chloride secretion but instead by the increase in sodium and water reabsorption.

This results in the deposition of thick, dehydrated mucus, which collects in the respiratory tract, interfering with gas exchange and allowing for the collection of bacteria.

Tracing timelines gives Spyryx clues to complex triggers 


First mention of Na+ absorption in PubMed
(Fleisher, Hoyt & Loeb)


Hans Ussing recognizes active Na+ transport
(across frog skin epithelia)


First publication of the ENaC antagonist amiloride
(Eigler J, Kelter J, Renner E)


John Gatzy at UNC is first person to measure ion transport in the lung
(Gatzy JT, AJP 1967)


Knowles/Boucher notice increased PDs across CF nasal mucosa


Boucher demonstrates increased Na+ transport in isolated CF epithelia


Bernard Rossier and colleagues clone ENaC subunits


Amiloride fails as a treatment for CF


Ric Lifton, Rossiers and colleagues identify ENaC as cause of Liddles, PHA


Bernard Rossier and colleagues clone channel activating protease 1


PLUNC 1st identified. Function unknown.
(Weston WM et al JBC 1999)


Peter Di’s group identify SPURT, which turns out to be PLUNC, and find that its expression is altered in COPD patients


ENaC overexpressing mouse shows spontaneous lung disease


PLUNC is found to be part of a larger family of related proteins and is renamed short PLUNC1 (SPLUNC1)


Tarran lab find SPLUNC1 to be a regulator of ENaC
(Garcia-Cabellero et al., PNAS)


SPLUNC1 protects ENaC from proteolytic cleavage.
(Cystic Fibrosis/Pulmonary Research and Treatment Center, UNC)


SPLUNC1 found to be part of an even larger family of proteins and renamed BPIFA1


SPLUNC1 is considered an innate material to help mucosa immunity
(Bingle L, Bingle)


Tarran lab identify SPLUNC1’s ENaC inhibitory domain
(S18) (Hobbs C et al,. AJP lung 2013


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