A dual Golgi- and mitochondria-localised Ala25Ser precursor cystatin C: An additional tool for characterising intracellular mis-localisation leading to increased AMD susceptibility
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- Dr Glyn Nelson
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| Author(s) | | Ratnayaka A, Paraoan L, Spiller DG, Hiscott P, Nelson G, White MRH, Grierson I |
| Publication type | | Letter |
| Journal | | Experimental Eye Research |
| Year | | 2007 |
| Volume | | 84 |
| Issue | | 6 |
| Pages | | 1135-1139 |
| ISSN (print) | | 0014-4835 |
| ISSN (electronic) | | 1096-0007 |
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| Full text for this publication is not currently held within this repository. Alternative links are provided below where available. |
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| 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) or serine is sufficient to impair the intracellular trafficking and processing of the protein. (c) 2006 Elsevier Ltd. All rights reserved. |
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| URL | | http://dx.doi.org/10.1016/j.exer.2006.01.030 |
| DOI | | 10.1016/j.exer.2006.01.030 |
| Notes | | 179HC
Times Cited:0
Cited References Count:16 |
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