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The human disease gene LYSET is essential for lysosomal enzyme transport and viral infection

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The human disease gene LYSET is essential for lysosomal enzyme transport and viral infection. / Richards, Christopher M; Jabs, Sabrina; Qiao, Wenjie; Varanese, Lauren D; Schweizer, Michaela; Mosen, Peter R; Riley, Nicholas M; Klüssendorf, Malte; Zengel, James R; Flynn, Ryan A; Rustagi, Arjun; Widen, John C; Peters, Christine E; Ooi, Yaw Shin; Xie, Xuping; Shi, Pei-Yong; Bartenschlager, Ralf; Puschnik, Andreas S; Bogyo, Matthew; Bertozzi, Carolyn R; Blish, Catherine A; Winter, Dominic; Nagamine, Claude M; Braulke, Thomas; Carette, Jan E.

In: SCIENCE, Vol. 378, No. 6615, eabn5648, 07.10.2022.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Richards, CM, Jabs, S, Qiao, W, Varanese, LD, Schweizer, M, Mosen, PR, Riley, NM, Klüssendorf, M, Zengel, JR, Flynn, RA, Rustagi, A, Widen, JC, Peters, CE, Ooi, YS, Xie, X, Shi, P-Y, Bartenschlager, R, Puschnik, AS, Bogyo, M, Bertozzi, CR, Blish, CA, Winter, D, Nagamine, CM, Braulke, T & Carette, JE 2022, 'The human disease gene LYSET is essential for lysosomal enzyme transport and viral infection', SCIENCE, vol. 378, no. 6615, eabn5648. https://doi.org/10.1126/science.abn5648

APA

Richards, C. M., Jabs, S., Qiao, W., Varanese, L. D., Schweizer, M., Mosen, P. R., Riley, N. M., Klüssendorf, M., Zengel, J. R., Flynn, R. A., Rustagi, A., Widen, J. C., Peters, C. E., Ooi, Y. S., Xie, X., Shi, P-Y., Bartenschlager, R., Puschnik, A. S., Bogyo, M., ... Carette, J. E. (2022). The human disease gene LYSET is essential for lysosomal enzyme transport and viral infection. SCIENCE, 378(6615), [eabn5648]. https://doi.org/10.1126/science.abn5648

Vancouver

Richards CM, Jabs S, Qiao W, Varanese LD, Schweizer M, Mosen PR et al. The human disease gene LYSET is essential for lysosomal enzyme transport and viral infection. SCIENCE. 2022 Oct 7;378(6615). eabn5648. https://doi.org/10.1126/science.abn5648

Bibtex

@article{af77475166c24035a2a5e1062f4e1926,
title = "The human disease gene LYSET is essential for lysosomal enzyme transport and viral infection",
abstract = "Lysosomes are key degradative compartments of the cell. Transport to lysosomes relies on GlcNAc-1-phosphotransferase-mediated tagging of soluble enzymes with mannose 6-phosphate (M6P). GlcNAc-1-phosphotransferase deficiency leads to the severe lysosomal storage disorder mucolipidosis II (MLII). Several viruses require lysosomal cathepsins to cleave structural proteins and thus depend on functional GlcNAc-1-phosphotransferase. We used genome-scale CRISPR screens to identify lysosomal enzyme trafficking factor (LYSET, also named TMEM251) as essential for infection by cathepsin-dependent viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). LYSET deficiency resulted in global loss of M6P tagging and mislocalization of GlcNAc-1-phosphotransferase from the Golgi complex to lysosomes. Lyset knockout mice exhibited MLII-like phenotypes, and human pathogenic LYSET alleles failed to restore lysosomal sorting defects. Thus, LYSET is required for correct functioning of the M6P trafficking machinery and mutations in LYSET can explain the phenotype of the associated disorder.",
keywords = "Animals, COVID-19/genetics, Cathepsins/metabolism, Humans, Lysosomes/metabolism, Mannose/metabolism, Mice, Mice, Knockout, Mucolipidoses/genetics, Proteins/genetics, Transferases (Other Substituted Phosphate Groups)",
author = "Richards, {Christopher M} and Sabrina Jabs and Wenjie Qiao and Varanese, {Lauren D} and Michaela Schweizer and Mosen, {Peter R} and Riley, {Nicholas M} and Malte Kl{\"u}ssendorf and Zengel, {James R} and Flynn, {Ryan A} and Arjun Rustagi and Widen, {John C} and Peters, {Christine E} and Ooi, {Yaw Shin} and Xuping Xie and Pei-Yong Shi and Ralf Bartenschlager and Puschnik, {Andreas S} and Matthew Bogyo and Bertozzi, {Carolyn R} and Blish, {Catherine A} and Dominic Winter and Nagamine, {Claude M} and Thomas Braulke and Carette, {Jan E}",
year = "2022",
month = oct,
day = "7",
doi = "10.1126/science.abn5648",
language = "English",
volume = "378",
journal = "SCIENCE",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6615",

}

RIS

TY - JOUR

T1 - The human disease gene LYSET is essential for lysosomal enzyme transport and viral infection

AU - Richards, Christopher M

AU - Jabs, Sabrina

AU - Qiao, Wenjie

AU - Varanese, Lauren D

AU - Schweizer, Michaela

AU - Mosen, Peter R

AU - Riley, Nicholas M

AU - Klüssendorf, Malte

AU - Zengel, James R

AU - Flynn, Ryan A

AU - Rustagi, Arjun

AU - Widen, John C

AU - Peters, Christine E

AU - Ooi, Yaw Shin

AU - Xie, Xuping

AU - Shi, Pei-Yong

AU - Bartenschlager, Ralf

AU - Puschnik, Andreas S

AU - Bogyo, Matthew

AU - Bertozzi, Carolyn R

AU - Blish, Catherine A

AU - Winter, Dominic

AU - Nagamine, Claude M

AU - Braulke, Thomas

AU - Carette, Jan E

PY - 2022/10/7

Y1 - 2022/10/7

N2 - Lysosomes are key degradative compartments of the cell. Transport to lysosomes relies on GlcNAc-1-phosphotransferase-mediated tagging of soluble enzymes with mannose 6-phosphate (M6P). GlcNAc-1-phosphotransferase deficiency leads to the severe lysosomal storage disorder mucolipidosis II (MLII). Several viruses require lysosomal cathepsins to cleave structural proteins and thus depend on functional GlcNAc-1-phosphotransferase. We used genome-scale CRISPR screens to identify lysosomal enzyme trafficking factor (LYSET, also named TMEM251) as essential for infection by cathepsin-dependent viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). LYSET deficiency resulted in global loss of M6P tagging and mislocalization of GlcNAc-1-phosphotransferase from the Golgi complex to lysosomes. Lyset knockout mice exhibited MLII-like phenotypes, and human pathogenic LYSET alleles failed to restore lysosomal sorting defects. Thus, LYSET is required for correct functioning of the M6P trafficking machinery and mutations in LYSET can explain the phenotype of the associated disorder.

AB - Lysosomes are key degradative compartments of the cell. Transport to lysosomes relies on GlcNAc-1-phosphotransferase-mediated tagging of soluble enzymes with mannose 6-phosphate (M6P). GlcNAc-1-phosphotransferase deficiency leads to the severe lysosomal storage disorder mucolipidosis II (MLII). Several viruses require lysosomal cathepsins to cleave structural proteins and thus depend on functional GlcNAc-1-phosphotransferase. We used genome-scale CRISPR screens to identify lysosomal enzyme trafficking factor (LYSET, also named TMEM251) as essential for infection by cathepsin-dependent viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). LYSET deficiency resulted in global loss of M6P tagging and mislocalization of GlcNAc-1-phosphotransferase from the Golgi complex to lysosomes. Lyset knockout mice exhibited MLII-like phenotypes, and human pathogenic LYSET alleles failed to restore lysosomal sorting defects. Thus, LYSET is required for correct functioning of the M6P trafficking machinery and mutations in LYSET can explain the phenotype of the associated disorder.

KW - Animals

KW - COVID-19/genetics

KW - Cathepsins/metabolism

KW - Humans

KW - Lysosomes/metabolism

KW - Mannose/metabolism

KW - Mice

KW - Mice, Knockout

KW - Mucolipidoses/genetics

KW - Proteins/genetics

KW - Transferases (Other Substituted Phosphate Groups)

U2 - 10.1126/science.abn5648

DO - 10.1126/science.abn5648

M3 - SCORING: Journal article

C2 - 36074821

VL - 378

JO - SCIENCE

JF - SCIENCE

SN - 0036-8075

IS - 6615

M1 - eabn5648

ER -