Mucolipidosis II‐Related Mutations Inhibit the Exit from the Endoplasmic Reticulum and Proteolytic Cleavage of GlcNAc‐1‐Phosphotransferase Precursor Protein (GNPTAB). Issue 3 (15th January 2014)

• Record Type: Journal Article
• Authors: De, Raffaella; Coutinho, Maria Francisca; Koch‐Nolte, Friedrich; Haag, Friedrich; Prata, Maria João; Alves, Sandra; Braulke, Thomas; Pohl, Sandra
• Is Part Of: Human mutation. Volume 35:Issue 3(2014:Mar.)
• Page Start: 368
• Page End: 376
• Publication Date: 2014-01-15
• Subjects: Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.22502
• Languages: English
• ISSNs: 1059-7794

Abstract

<abstract abstract-type="graphical" xml:lang="en" id="humu22502-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The lysosomal disorder mucolipidosis II (MLII) is caused by mutations in GNPTAB encoding an α/β‐subunit precursor protein of the oligomeric Golgi‐resident GlcNAc‐1‐phosphotransferase. This enzyme forms mannose 6‐phosphate targeting signals on lysosomal enzymes prerequisite for lysosomal function. Here, we analyzed the expression of six missense and frameshift mutations identified in patients and found that they either affect ER‐Golgi transport, site‐1 protease mediated proteolytic activation or mRNA stability of the α/β‐subunit precursor protein, and associate with different clinical courses of the disease <boxed-text content-type="graphic" position="anchor" orientation="portrait"><graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pgg4stk8vnx" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /></boxed-text></p> </abstract>