A dual Golgi- and mitochondria-localised Ala25Ser precursor cystatin C: an additional tool for characterising intracellular mis-localisation leading to increased AMD susceptibility.

Experimental Eye Research
Arjuna RatnayakaIan Grierson

Abstract

An artificial mutant Ala25Ser precursor cystatin C was created to help elucidate the cause of intracellular mis-localisation of the biochemically related variant B (Ala25Thr) precursor cystatin C to the mitochondria. Homozygotes of variant B precursor cystatin C were reported to carry an increased susceptibility to developing the exudative form of AMD. Ala25Ser precursor cystatin C shows a dual distribution to the Golgi apparatus and to the mitochondria. This localisation is thus intermediary between that of wild-type cystatin C (targeted to ER/Golgi compartment) and that of variant B precursor cystatin C. Furthermore, the level of secretion of Ala25Ser cystatin C by RPE cells is intermediary between wild type and variant B cystatin C. Ala25Ser precursor cystatin C thus represents a biochemical intermediate between the wild type and the AMD-associated cystatin C and as such, is a novel tool for the investigation of the mechanism of intracellular mis-localisation of variant B cystatin C. Our findings further support the hypothesis that substitution of the alanine residue in the penultimate position of precursor cystatin C signal sequence with a less hydrophobic amino acid residue, such as threonine (as in variant B cystatin C) o...Continue Reading

References

Jul 22, 1991·FEBS Letters·V Turk, W Bode
Jun 1, 1990·The Biochemical Journal·M AbrahamsonA Grubb
Apr 13, 2000·The International Journal of Biochemistry & Cell Biology·L ParaoanB E Maden
Jan 30, 2002·The British Journal of Ophthalmology·Jan ZurdelGisbert Richard
Feb 16, 2002·Bioinformatics·Hideo BannaiSatoru Miyano

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Citations

May 30, 2017·Neural Regeneration Research·Savannah A LynnJ Arjuna Ratnayaka
Feb 13, 2020·Investigative Ophthalmology & Visual Science·Emil CarlssonLuminita Paraoan
Apr 17, 2020·Progress in Retinal and Eye Research·Kai KaarnirantaDeborah Ferrington
Apr 13, 2020·Progress in Retinal and Eye Research·Luminita ParaoanIan Grierson

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