The SHDRA syndrome-associated gene TMEM260 encodes a protein-specific O-mannosyltransferase

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

Standard

The SHDRA syndrome-associated gene TMEM260 encodes a protein-specific O-mannosyltransferase. / Larsen, Ida Signe Bohse; Povolo, Lorenzo; Zhou, Luping; Tian, Weihua; Mygind, Kasper Johansen; Hintze, John; Jiang, Chen; Hartill, Verity; Prescott, Katrina; Johnson, Colin A.; Mullegama, Sureni V.; McConkie-Rosell, Allyn; McDonald, Marie; Hansen, Lars; Vakhrushev, Sergey Y.; Schjoldager, Katrine T.; Clausen, Henrik; Worzfeld, Thomas; Joshi, Hiren J.; Halim, Adnan.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 120, No. 21, 2023, p. e2302584120.

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

Harvard

Larsen, ISB, Povolo, L, Zhou, L, Tian, W, Mygind, KJ, Hintze, J, Jiang, C, Hartill, V, Prescott, K, Johnson, CA, Mullegama, SV, McConkie-Rosell, A, McDonald, M, Hansen, L, Vakhrushev, SY, Schjoldager, KT, Clausen, H, Worzfeld, T, Joshi, HJ & Halim, A 2023, 'The SHDRA syndrome-associated gene TMEM260 encodes a protein-specific O-mannosyltransferase', Proceedings of the National Academy of Sciences of the United States of America, vol. 120, no. 21, pp. e2302584120. https://doi.org/10.1073/pnas.2302584120

APA

Larsen, I. S. B., Povolo, L., Zhou, L., Tian, W., Mygind, K. J., Hintze, J., Jiang, C., Hartill, V., Prescott, K., Johnson, C. A., Mullegama, S. V., McConkie-Rosell, A., McDonald, M., Hansen, L., Vakhrushev, S. Y., Schjoldager, K. T., Clausen, H., Worzfeld, T., Joshi, H. J., & Halim, A. (2023). The SHDRA syndrome-associated gene TMEM260 encodes a protein-specific O-mannosyltransferase. Proceedings of the National Academy of Sciences of the United States of America, 120(21), e2302584120. https://doi.org/10.1073/pnas.2302584120

Vancouver

Larsen ISB, Povolo L, Zhou L, Tian W, Mygind KJ, Hintze J et al. The SHDRA syndrome-associated gene TMEM260 encodes a protein-specific O-mannosyltransferase. Proceedings of the National Academy of Sciences of the United States of America. 2023;120(21):e2302584120. https://doi.org/10.1073/pnas.2302584120

Author

Larsen, Ida Signe Bohse ; Povolo, Lorenzo ; Zhou, Luping ; Tian, Weihua ; Mygind, Kasper Johansen ; Hintze, John ; Jiang, Chen ; Hartill, Verity ; Prescott, Katrina ; Johnson, Colin A. ; Mullegama, Sureni V. ; McConkie-Rosell, Allyn ; McDonald, Marie ; Hansen, Lars ; Vakhrushev, Sergey Y. ; Schjoldager, Katrine T. ; Clausen, Henrik ; Worzfeld, Thomas ; Joshi, Hiren J. ; Halim, Adnan. / The SHDRA syndrome-associated gene TMEM260 encodes a protein-specific O-mannosyltransferase. In: Proceedings of the National Academy of Sciences of the United States of America. 2023 ; Vol. 120, No. 21. pp. e2302584120.

Bibtex

@article{37ed94837df34710afceda630b828289,
title = "The SHDRA syndrome-associated gene TMEM260 encodes a protein-specific O-mannosyltransferase",
abstract = "Mutations in the TMEM260 gene cause structural heart defects and renal anomalies syndrome, but the function of the encoded protein remains unknown. We previously reported wide occurrence of O-mannose glycans on extracellular immunoglobulin, plexin, transcription factor (IPT) domains found in the hepatocyte growth factor receptor (cMET), macrophage-stimulating protein receptor (RON), and plexin receptors, and further demonstrated that two known protein O-mannosylation systems orchestrated by the POMT1/2 and transmembrane and tetratricopeptide repeat-containing proteins 1-4 gene families were not required for glycosylation of these IPT domains. Here, we report that the TMEM260 gene encodes an ER-located protein O-mannosyltransferase that selectively glycosylates IPT domains. We demonstrate that disease-causing TMEM260 mutations impair O-mannosylation of IPT domains and that TMEM260 knockout in cells results in receptor maturation defects and abnormal growth of 3D cell models. Thus, our study identifies the third protein-specific O-mannosylation pathway in mammals and demonstrates that O-mannosylation of IPT domains serves critical functions during epithelial morphogenesis. Our findings add a new glycosylation pathway and gene to a growing group of congenital disorders of glycosylation.",
keywords = "congenital disorders of glycosylation, glycoproteomics, glycosylation, O-mannosylation, plexin",
author = "Larsen, {Ida Signe Bohse} and Lorenzo Povolo and Luping Zhou and Weihua Tian and Mygind, {Kasper Johansen} and John Hintze and Chen Jiang and Verity Hartill and Katrina Prescott and Johnson, {Colin A.} and Mullegama, {Sureni V.} and Allyn McConkie-Rosell and Marie McDonald and Lars Hansen and Vakhrushev, {Sergey Y.} and Schjoldager, {Katrine T.} and Henrik Clausen and Thomas Worzfeld and Joshi, {Hiren J.} and Adnan Halim",
year = "2023",
doi = "10.1073/pnas.2302584120",
language = "English",
volume = "120",
pages = "e2302584120",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "The National Academy of Sciences of the United States of America",
number = "21",

}

RIS

TY - JOUR

T1 - The SHDRA syndrome-associated gene TMEM260 encodes a protein-specific O-mannosyltransferase

AU - Larsen, Ida Signe Bohse

AU - Povolo, Lorenzo

AU - Zhou, Luping

AU - Tian, Weihua

AU - Mygind, Kasper Johansen

AU - Hintze, John

AU - Jiang, Chen

AU - Hartill, Verity

AU - Prescott, Katrina

AU - Johnson, Colin A.

AU - Mullegama, Sureni V.

AU - McConkie-Rosell, Allyn

AU - McDonald, Marie

AU - Hansen, Lars

AU - Vakhrushev, Sergey Y.

AU - Schjoldager, Katrine T.

AU - Clausen, Henrik

AU - Worzfeld, Thomas

AU - Joshi, Hiren J.

AU - Halim, Adnan

PY - 2023

Y1 - 2023

N2 - Mutations in the TMEM260 gene cause structural heart defects and renal anomalies syndrome, but the function of the encoded protein remains unknown. We previously reported wide occurrence of O-mannose glycans on extracellular immunoglobulin, plexin, transcription factor (IPT) domains found in the hepatocyte growth factor receptor (cMET), macrophage-stimulating protein receptor (RON), and plexin receptors, and further demonstrated that two known protein O-mannosylation systems orchestrated by the POMT1/2 and transmembrane and tetratricopeptide repeat-containing proteins 1-4 gene families were not required for glycosylation of these IPT domains. Here, we report that the TMEM260 gene encodes an ER-located protein O-mannosyltransferase that selectively glycosylates IPT domains. We demonstrate that disease-causing TMEM260 mutations impair O-mannosylation of IPT domains and that TMEM260 knockout in cells results in receptor maturation defects and abnormal growth of 3D cell models. Thus, our study identifies the third protein-specific O-mannosylation pathway in mammals and demonstrates that O-mannosylation of IPT domains serves critical functions during epithelial morphogenesis. Our findings add a new glycosylation pathway and gene to a growing group of congenital disorders of glycosylation.

AB - Mutations in the TMEM260 gene cause structural heart defects and renal anomalies syndrome, but the function of the encoded protein remains unknown. We previously reported wide occurrence of O-mannose glycans on extracellular immunoglobulin, plexin, transcription factor (IPT) domains found in the hepatocyte growth factor receptor (cMET), macrophage-stimulating protein receptor (RON), and plexin receptors, and further demonstrated that two known protein O-mannosylation systems orchestrated by the POMT1/2 and transmembrane and tetratricopeptide repeat-containing proteins 1-4 gene families were not required for glycosylation of these IPT domains. Here, we report that the TMEM260 gene encodes an ER-located protein O-mannosyltransferase that selectively glycosylates IPT domains. We demonstrate that disease-causing TMEM260 mutations impair O-mannosylation of IPT domains and that TMEM260 knockout in cells results in receptor maturation defects and abnormal growth of 3D cell models. Thus, our study identifies the third protein-specific O-mannosylation pathway in mammals and demonstrates that O-mannosylation of IPT domains serves critical functions during epithelial morphogenesis. Our findings add a new glycosylation pathway and gene to a growing group of congenital disorders of glycosylation.

KW - congenital disorders of glycosylation

KW - glycoproteomics

KW - glycosylation

KW - O-mannosylation

KW - plexin

U2 - 10.1073/pnas.2302584120

DO - 10.1073/pnas.2302584120

M3 - Journal article

C2 - 37186866

AN - SCOPUS:85159499805

VL - 120

SP - e2302584120

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 21

ER -

ID: 347698499