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Please use this identifier to cite or link to this item: http://hdl.handle.net/10400.18/508

Título: Mannose-6-phosphate pathway: A review on its role in lysosomal function and dysfunction.
Autor: Coutinho, Maria Francisca
Prata, Maria João
Alves, Sandra
Palavras-chave: Mannose-6-phosphate-dependent Pathway
GlcNAc-1-phosphotransferase
Uncovering enzyme (UCE)
Mannose-6-phosphate Receptors
Mucolipidosis Type II (I-cell disease)
Mucolipidosis Type III (Pseudo-Hurler disease)
Doenças Genéticas
Issue Date: 23-Dec-2011
Editora: Elsevier
Citação: Mol Genet Metab. 2011 Dec 23. [Epub ahead of print]
Resumo: Lysosomal hydrolases are synthesized in the rough endoplasmic reticulum and specifically transported through the Golgi apparatus to the trans-Golgi network, from which transport vesicles bud to deliver them to the endosomal/lysosomal compartment. The explanation of how are the lysosomal enzymes accurately recognized and selected over many other proteins in the trans-Golgi network relies on being tagged with a unique marker: the mannose-6-phosphate (M6P) group, which is added exclusively to the N-linked oligosaccharides of lysosomal soluble hydrolases, as they pass through the cis-Golgi network. Generation of the M6P recognition marker depends on a reaction involving two different enzymes: UDP-N-acetylglucosamine 1-phosphotransferase and α-N-acetylglucosamine-1-phosphodiester α-N-acetylglucosaminidase. The M6P groups are then recognized by two independent transmembrane M6P receptors, present in the trans-Golgi network: the cation-independent M6P receptor and/or the cation-dependent M6P receptor. These proteins bind to lysosomal hydrolases on the lumenal side of the membrane and to adaptins in assembling clathrin coats on the cytosolic side. In this way, the M6P receptors help package the hydrolases into vesicles that bud from the trans-Golgi network to deliver their contents to endosomes that ultimately will develop into mature lysosomes, where recently-delivered hydrolases may start digesting the endocyted material. The above described process is known as the M6P-dependent pathway and is responsible for transporting most lysosomal enzymes. This review synthesizes the current knowledge on each of the major proteins involved in the M6P-dependent pathway. Impairments in this pathway will also be addressed, highlighting the lysosomal storage disorders associated to GlcNAc-1-phosphotransferase loss of function: mucolipidosis type II and III.
Arbitragem científica: yes
URI: http://hdl.handle.net/10400.18/508
Versão do Editor: http://www.sciencedirect.com/science/article/pii/S1096719211006524
Appears in Collections:DGH - Artigos em revistas internacionais

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