Evidence map›Paper›PMID 39677738›Full record

ArticlebioRxiv : the preprint server for biology2024

Molecular Insights into the Regulation of GNPTAB by TMEM251.

Xi Yang, Balraj Doray, Varsha Venkatarangan, Benjamin C Jennings, Danielle Henn, Jiaxuan Liang, Haikun Zhao, Weichao Zhang, Bokai Zhang, Linchen Yu and 3 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Xi YangDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Balraj DorayDepartment of Internal Medicine, Washington University School of Medicine, St. Louis, Mo 63110, USA.
Varsha VenkataranganDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Benjamin C JenningsDepartment of Internal Medicine, Washington University School of Medicine, St. Louis, Mo 63110, USA.
Danielle HennDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Jiaxuan LiangDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Haikun ZhaoDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Weichao ZhangDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Bokai ZhangDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Linchen YuDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Liang ChenDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Stuart KornfeldDepartment of Internal Medicine, Washington University School of Medicine, St. Louis, Mo 63110, USA.
Ming LiDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.

Funding

Structure, Biosynthesis & Function of GlycoproteinsR01CA008759 · NCI · WASHINGTON UNIVERSITY · PI KORNFELD, STUART A · 1985 to 2023
$3.5M
Characterization of TMEM251 that causes a new type of severe lysosome storage diseaseR01HD109346 · NICHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Ming Li · 2022 to 2026
$2.1M
NCI NIH HHS R01 CA008759NICHD NIH HHS R01 HD109346
6 · The paper itself

Abstract

In vertebrates, newly synthesized lysosomal enzymes traffick to lysosomes through the mannose-6-phosphate (M6P) pathway. The Golgi membrane protein TMEM251 was recently discovered to regulate lysosome biogenesis by controlling the level of GlcNAc-1-phosphotransferase (GNPT). However, its precise function remained unclear. In this study, we demonstrate that TMEM251 is a two-transmembrane protein indispensable for GNPT stability, cleavage by Site-1-Protease (S1P), and enzymatic activity. We reconcile conflicting models by showing that TMEM251 enhances GNPT cleavage and prevents its mislocalization to lysosomes for degradation. We further establish that TMEM251 achieves this by interacting with GOLPH3 and retromer complexes to anchor the TMEM251-GNPT complex at the Golgi. Alanine mutagenesis identified F

Indexed as

GNPTGolgilysosomeMLIIMLVMucolipidosisTMEM251/LYSET/GCAF

Identifiers

PMID39677738
PMCPMC11643035

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.