GCAF(TMEM251) regulates lysosome biogenesis by activating the mannose-6-phosphate pathway

Weichao Zhang; Xi Yang; Yingxiang Li; Linchen Yu; Bokai Zhang; Jianchao Zhang; Woo Jung Cho; Varsha Venkatarangan; Liang Chen; Bala Bharathi Burugula; Sarah Bui; Yanzhuang Wang; Cunming Duan; Jacob O. Kitzman; Ming Li

doi:10.1038/s41467-022-33025-1

Nature Communications (Sep 2022)

GCAF(TMEM251) regulates lysosome biogenesis by activating the mannose-6-phosphate pathway

Weichao Zhang,
Xi Yang,
Yingxiang Li,
Linchen Yu,
Bokai Zhang,
Jianchao Zhang,
Woo Jung Cho,
Varsha Venkatarangan,
Liang Chen,
Bala Bharathi Burugula,
Sarah Bui,
Yanzhuang Wang,
Cunming Duan,
Jacob O. Kitzman,
Ming Li

Affiliations

Weichao Zhang: Department of Molecular, Cellular, and Developmental Biology, University of Michigan
Xi Yang: Department of Molecular, Cellular, and Developmental Biology, University of Michigan
Yingxiang Li: Department of Molecular, Cellular, and Developmental Biology, University of Michigan
Linchen Yu: Department of Molecular, Cellular, and Developmental Biology, University of Michigan
Bokai Zhang: Department of Molecular, Cellular, and Developmental Biology, University of Michigan
Jianchao Zhang: Department of Molecular, Cellular, and Developmental Biology, University of Michigan
Woo Jung Cho: BRCF Microscopy Core, University of Michigan Medical School
Varsha Venkatarangan: Department of Molecular, Cellular, and Developmental Biology, University of Michigan
Liang Chen: Department of Molecular, Cellular, and Developmental Biology, University of Michigan
Bala Bharathi Burugula: Department of Human Genetics, University of Michigan Medical School
Sarah Bui: Department of Molecular, Cellular, and Developmental Biology, University of Michigan
Yanzhuang Wang: Department of Molecular, Cellular, and Developmental Biology, University of Michigan
Cunming Duan: Department of Molecular, Cellular, and Developmental Biology, University of Michigan
Jacob O. Kitzman: Department of Human Genetics, University of Michigan Medical School
Ming Li: Department of Molecular, Cellular, and Developmental Biology, University of Michigan

DOI: https://doi.org/10.1038/s41467-022-33025-1
Journal volume & issue: Vol. 13, no. 1
pp. 1 – 17

Abstract

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Lysosomal biogenesis errors often result in diseases including mucolipidosis. Here Zhang and Yang et al. identify TMEM251/GCAF as a mannose-6-phosphate modification regulator that is necessary for correct lysosomal targeting, and classify Mucolipidosis Type V as resulting from GCAF mutations.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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