Mannose-6-phosphate pathway: A review on its role in lysosomal function and dysfunction

Coutinho, Maria Francisca; Prata, Maria João; Alves, Sandra

doi:10.1016/j.ymgme.2011.12.012

Cited by 197 publications

(169 citation statements)

References 85 publications

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“…This is an example of microbial eukaryotic phosphoglycosylation, as reported in some slime molds and unicellular parasites (42). Although mannose-6-phosphate modification has a role in the targeting of lysosome-resident enzymes to the lysosome in mammalian cells (43), this appears to be a modification of more-complex (high-mannose) glycans, that are exclusively N linked (43). Overall, PhosphoHex-modified peptides [PhosphoHex and PhosphoHex (2)] seemed quite plentiful in blind modification search results (Table S20).…”

Section: Fig 2 Confidently Identified Vaccinia Virus and Host Proteinmentioning

confidence: 78%

Protein Primary Structure of the Vaccinia Virion at Increased Resolution

Ngo

Mirzakhanyan

Moussatché

et al. 2016

J Virol

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Here we examine the protein covalent structure of the vaccinia virus virion. Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. We also detected the expression of four short ORFs, each of which was located within an ORF ("ORF-within-ORF"), including one not previously recognized or known to be expressed. Using quantitative mass spectrometry (MS), between 58 and 74 proteins were determined to be packaged. A total of 63 host proteins were also identified as candidates for packaging. Evidence is provided that some portion of virion proteins are "nicked" via a combination of endoproteolysis and concerted exoproteolysis in a manner, and at sites, IMPORTANCEPoxviruses are among the most complex and irregular virions, about whose internal structure little is known. To better understand poxvirus virion structure, imaging should be supplemented with other tools. Here, we provide a deep study of the covalent structure of the vaccinia virus virion using the various tools of contemporary mass spectrometry. C ontemporary mass spectrometry (MS) instrumentation provides an avenue for proteome coverage with enormous breadth or depth, depending upon the complexity of the proteome. Typically, the power of the approach is exploited for breadth in the analysis of increasingly complex proteomes. Here, we have taken a relatively narrow proteome, that of a virus particle, and explored proteome depth, developing analytical approaches and tools as required.Sporadic information is available on the covalent (primary) molecular structure of the vaccinia virus virion. Around 75 proteins can be detected in two-dimensional (2D) gels of purified vaccinia virus virions (1). Three published MS studies provided early compendia of viral and host gene products present within vaccinia virus and human monkeypox virion preparations via MS (2-5). These studies built upon earlier, less comprehensive studies that employed a combination of MS and N-terminal sequencing (1, 6). Overlapping approaches in terms of instrumentation, preparation, and data analysis led to an overlapping set of detected gene products.In terms of covalent protein modifications, six vaccinia virus proteins can be labeled in vivo with myristate, five of which have been identified as L1R (7,8), G9R, A16L, and E7R (9), and A14L (10). All except A14L possess a glycine at position 2 in the protein.At least eight vaccinia virus-encoded proteins may be palmitoylated, as evidenced by the incorporation of 3 H-labeled palmitate in culture (11). These proteins include wrapped virus (WV)-specific protein p37 (F13L) (7,(12)(13)(14) and products of open reading frames (ORFs) A33R (15), B5R (16), F13L (17), the A22R Holliday resolvase (11), A...

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Section: Fig 2 Confidently Identified Vaccinia Virus and Host Proteinmentioning

confidence: 78%

Protein Primary Structure of the Vaccinia Virion at Increased Resolution

Ngo

Mirzakhanyan

Moussatché

et al. 2016

J Virol

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“…For example, retromer-mediated lysosomal receptors recycling, such as the mannose-6-phosphate receptor (MPR), maintains sufficient delivery of hydrolases for lysosomal function. In the absence of functional retromer, autophagy and lysosomal degradative capacity are perturbed leading to abnormal accumulation of material in lysosomes and lysosomal storage diseases [105]. The lysosomes are also of vital importance to the cell as they can trigger apoptotic cell death when their integrity or functions are compromised [106][107][108].…”

Section: Snx1 and Snx2mentioning

confidence: 99%

Caspases rule the intracellular trafficking cartel

2017

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During apoptosis, caspases feast on several hundreds of cellular proteins to orchestrate rapid cellular demise. Indeed, caspases are known to get a taste of every cellular process in one way or another, activating some, but most often shutting them down. Thus, it is not surprising that caspases proteolyze proteins involved in intracellular trafficking with particularly devastating consequences for this important process. This review article focuses on how caspases target the machinery responsible for smuggling goods within and outside the cell.

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“…This modification is highly dynamic and reversible. At the cis-Golgi level, phosphorylation of mannose residues carried by newly synthesized lysosomal enzymes is a crucial step for their recognition by mannose-6-phosphate receptors and their correct targeting to lysosomes (Braulke and Bonifacino 2009;Coutinho et al 2012). Phosphorylation at the Golgi level also occurs via FAM20C on secretory calciumbinding phosphoproteins (SCPP) family (including casein) and many secreted proteins involved in biomineralization, including the small integrin binding ligand N-linked glycoproteins (SIBLING proteins) (Nalbant et al 2005;Tagliabracci et al 2012).…”

Section: Phosphorylationmentioning

confidence: 99%

Golgi post‐translational modifications and associated diseases

Potelle

Klein

Foulquier

2015

J of Inher Metab Disea

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For non specialists, Golgi is a very well known subcellular compartment involved in secretion and correct targeting of soluble and transmembrane proteins. Nevertheless, Golgi is also specifically involved in many different and diverse post-translational modifications. Through its diverse functions, Golgi is not only able to modify secreted and transmembrane proteins but also cytoplasmic proteins. The Golgi apparatus research field is so broad that an exhaustive review of this organelle is not doable here. The goal of this review is to cover the main post-translational modifications occurring at the Golgi level and present the identified associated diseases.

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Mannose-6-phosphate pathway: A review on its role in lysosomal function and dysfunction

Cited by 197 publications

References 85 publications

Protein Primary Structure of the Vaccinia Virion at Increased Resolution

Protein Primary Structure of the Vaccinia Virion at Increased Resolution

Caspases rule the intracellular trafficking cartel

Golgi post‐translational modifications and associated diseases

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