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Durham University

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Publication details for Dr Martin Goldberg

Tapodi, Antal, Clemens, Daniel, Uwineza, Alice, Goldberg, Martin, Thinon, Emmanuelle, Heal, William, Tate, Edward, Nemeth-Cahalan, Karinne, Vorontsova, Irene, Jarrin, Miguel, Hall, James & Quinlan, Roy (2019). BFSP1 C-terminal domains released by post-translational processing events can alter significantly the calcium regulation of AQP0 water permeability. Experimental Eye Research 185: 107585.

Author(s) from Durham


BFSP1 (beaded filament structural protein 1, filensin) is a cytoskeletal protein expressed in the eye lens. It binds AQP0 in vitro and its C-terminal sequences have been suggested to regulate the water channel activity of AQP0. A myristoylated fragment from the C-terminus of BFSP1 was found in AQP0 enriched fractions. Here we identify BFSP1 as a substrate for caspase-mediated cleavage at several C-terminal sites including D433. Cleavage at D433 exposes a cryptic myristoylation sequence (434–451). We confirm that this sequence is an excellent substrate for both NMT1 and 2 (N-myristoyl transferase). Thus caspase cleavage may promote formation of myristoylated fragments derived from the BFSP1 C-terminus (G434-S665). Myristoylation at G434 was, however, not required for plasma membrane association, but biochemical fractionation and immunogold labeling confirmed that C-terminal BFSP1 fragments containing the myristoylation sequence colocalised with AQP0 in the same plasma membrane compartments of lens fibre cells. To determine the functional significance of the association of BFSP1 G434-S665 sequences with AQP0, we measured AQP0 water permeability in Xenopus oocytes co-transfected with transcripts expressing both AQP0 and various naturally occurring C-terminus fragments of BFSP1. We found that different fragments dramatically alter the response of AQP0 to different concentrations of Ca2+. The full-length C-terminal fragment (G434-S665) eliminates calcium regulation altogether. Shorter fragments enhance regulation by elevated calcium or reverse the wild type response. In particular, elimination of the myristoylation site by the mutation G434A reverses the order of water permeability sensitivity to different Ca2+ concentrations.