Tyrosinase and ocular diseases: Some novel thoughts on the molecular basis of oculocutaneous albinism type 1
Metadata of CSIR Papers
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| Title |
Tyrosinase and ocular diseases: Some novel thoughts on the molecular basis of oculocutaneous albinism type 1
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| Creator |
Ray, K
Chaki, M Sengupta, M |
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| Subject |
Ophthalmology
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| Description |
Tyrosinase (TYR) is a multifunctional copper-containing glycoenzyme (similar to 80 kDa), which plays a key role in the rate-limiting steps of the melanin biosynthetic pathway. This membrane-bound protein, possibly evolved by the fusion of two different copper-binding proteins, is mainly expressed in epidermal, ocular and follicular melanocytes. In the melanocytes, TYR functions as an integrated unit with other TYR-related proteins (TYRP1, TYRP2), lysosome-associated membrane protein 1 (LAMP1) and melanocyte-stimulating hormone receptors; thus forming a melanogenic complex. Mutations in the TYR gene (TYR, 11q14-21, MIM 606933) cause oculocutaneous albinism type 1 (OCA 1, MIM 203100), a developmental disorder having an autosomal recessive mode of inheritance. In addition, TYR can act as a modifier locus for primary congenital glaucoma (PCG) and it also contributes significantly in the eye developmental process. Expression of TYR during neuroblast division helps in later pathfinding by retinal ganglion cells from retina to the dorsal lateral geniculate nucleus. However, mutation screening of TYR is complicated by the presence of a pseudogene-TYR like segment (TYRL, 11p11.2, MIM 191270), sharing similar to 98% sequence identity with the 3 ' region of TYR. Thus, in absence of a full-proof strategy, any nucleotide variants identified in the 3 ' region of TYR could actually be present in TYRL. Interestingly, despite extensive search, the second TYR mutation in 15% of the OCA I cases remains unidentified. Several possible locations of these "uncharacterized mutations" (UCMs) have been speculated so far. Based on the structure of TYR gene, its sequence context and some experimental evidences, we propose two additional possibilities, which on further investigations might shed light on the molecular basis of UCMs in TYR of OCA I patients; (i) partial deletion of the exons 4 and 5 region of TYR that is homologous with TYRL and (ii) variations in the polymorphic GA complex repeat located between distal and proximal elements of the human TYR promoter that can modulate the expression of the gene leading to disease pathogenesis. (c) 2007 Elsevier Ltd. All rights reserved.
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| Publisher |
PERGAMON-ELSEVIER SCIENCE LTDOXFORDTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
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| Date |
2011-09-20T12:12:33Z
2011-09-20T12:12:33Z 2007 |
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| Type |
Review
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| Identifier |
PROGRESS IN RETINAL AND EYE RESEARCH
1350-9462 http://hdl.handle.net/123456789/14319 |
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| Language |
English
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