Alternative splicing encodes functional intracellular CD59 isoforms that mediate insulin secretion and are down-regulated in diabetic islets

Ewelina Golec; Alexander Ekström; Maciej Noga; Muhmmad Omar-Hmeadi; Per-Eric Lund; Bruno O Villoutreix; Ulrika Krus; Katarzyna Wozniak; Olle Korsgren; Erik Renström; Sebastian Barg; Ben C King; Anna M Blom

doi:10.1073/pnas.2120083119

Alternative splicing encodes functional intracellular CD59 isoforms that mediate insulin secretion and are down-regulated in diabetic islets

Ewelina Golec, Alexander Ekström, Maciej Noga, Muhmmad Omar-Hmeadi, Per-Eric Lund, Bruno O Villoutreix, Ulrika Krus, Katarzyna Wozniak, Olle Korsgren, Erik Renström, Sebastian Barg, Ben C King, Anna M Blom

Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review

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Significance This project describes the existence of previously unknown non-GPI-anchored CD59 isoforms required for insulin secretion, named CD59-IRIS-1 and CD59-IRIS-2, and finds reduced expression of CD59-IRIS isoforms in human diabetic islets, showing a link between dysregulation of IRIS isoforms and defects in insulin secretion in diabetic patients. These data open a path for future studies into CD59-IRIS expression and function in additional cell types capable of regulated secretion. Identification of additional specific CD59-IRIS binding partners within the cell could provide therapeutic targets for enhancement of insulin secretion in T2D.

Originalspråk	engelska
Antal sidor	10
Tidskrift	Proceedings of the National Academy of Sciences of the United States of America
Volym	119
Nummer	24
Tidigt onlinedatum	2022 juni 14
DOI	https://doi.org/10.1073/pnas.2120083119
Status	Published - 2022

Ämnesklassifikation (UKÄ)

Endokrinologi och diabetes

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10.1073/pnas.2120083119Licens: CC BY-NC-ND

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Golec, E., Ekström, A., Noga, M., Omar-Hmeadi, M., Lund, P-E., Villoutreix, B. O., Krus, U., Wozniak, K., Korsgren, O., Renström, E., Barg, S., King, B. C., & Blom, A. M. (2022). Alternative splicing encodes functional intracellular CD59 isoforms that mediate insulin secretion and are down-regulated in diabetic islets. Proceedings of the National Academy of Sciences of the United States of America, 119(24 ). https://doi.org/10.1073/pnas.2120083119

@article{4d6470f26d7747f2b366aea95a54bc43,

title = "Alternative splicing encodes functional intracellular CD59 isoforms that mediate insulin secretion and are down-regulated in diabetic islets",

abstract = "Significance This project describes the existence of previously unknown non-GPI-anchored CD59 isoforms required for insulin secretion, named CD59-IRIS-1 and CD59-IRIS-2, and finds reduced expression of CD59-IRIS isoforms in human diabetic islets, showing a link between dysregulation of IRIS isoforms and defects in insulin secretion in diabetic patients. These data open a path for future studies into CD59-IRIS expression and function in additional cell types capable of regulated secretion. Identification of additional specific CD59-IRIS binding partners within the cell could provide therapeutic targets for enhancement of insulin secretion in T2D.",

keywords = "Alternative Splicing, CD59 Antigens/genetics, Diabetes Mellitus/genetics, Humans, Insulin Secretion, Protein Isoforms/genetics",

author = "Ewelina Golec and Alexander Ekstr{\"o}m and Maciej Noga and Muhmmad Omar-Hmeadi and Per-Eric Lund and Villoutreix, {Bruno O} and Ulrika Krus and Katarzyna Wozniak and Olle Korsgren and Erik Renstr{\"o}m and Sebastian Barg and King, {Ben C} and Blom, {Anna M}",

year = "2022",

doi = "10.1073/pnas.2120083119",

language = "English",

volume = "119",

journal = "Proceedings of the National Academy of Sciences",

issn = "1091-6490",

publisher = "National Academy of Sciences",

number = "24 ",

}

Golec, E , Ekström, A, Noga, M, Omar-Hmeadi, M, Lund, P-E, Villoutreix, BO, Krus, U, Wozniak, K, Korsgren, O, Renström, E, Barg, S, King, BC & Blom, AM 2022, 'Alternative splicing encodes functional intracellular CD59 isoforms that mediate insulin secretion and are down-regulated in diabetic islets', Proceedings of the National Academy of Sciences of the United States of America, vol. 119, nr. 24 . https://doi.org/10.1073/pnas.2120083119

Alternative splicing encodes functional intracellular CD59 isoforms that mediate insulin secretion and are down-regulated in diabetic islets. / Golec, Ewelina ; Ekström, Alexander; Noga, Maciej et al.

I: Proceedings of the National Academy of Sciences of the United States of America, Vol. 119, Nr. 24 , 2022.

Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review

TY - JOUR

T1 - Alternative splicing encodes functional intracellular CD59 isoforms that mediate insulin secretion and are down-regulated in diabetic islets

AU - Golec, Ewelina

AU - Ekström, Alexander

AU - Noga, Maciej

AU - Omar-Hmeadi, Muhmmad

AU - Lund, Per-Eric

AU - Villoutreix, Bruno O

AU - Krus, Ulrika

AU - Wozniak, Katarzyna

AU - Korsgren, Olle

AU - Renström, Erik

AU - Barg, Sebastian

AU - King, Ben C

AU - Blom, Anna M

PY - 2022

Y1 - 2022

N2 - Significance This project describes the existence of previously unknown non-GPI-anchored CD59 isoforms required for insulin secretion, named CD59-IRIS-1 and CD59-IRIS-2, and finds reduced expression of CD59-IRIS isoforms in human diabetic islets, showing a link between dysregulation of IRIS isoforms and defects in insulin secretion in diabetic patients. These data open a path for future studies into CD59-IRIS expression and function in additional cell types capable of regulated secretion. Identification of additional specific CD59-IRIS binding partners within the cell could provide therapeutic targets for enhancement of insulin secretion in T2D.

AB - Significance This project describes the existence of previously unknown non-GPI-anchored CD59 isoforms required for insulin secretion, named CD59-IRIS-1 and CD59-IRIS-2, and finds reduced expression of CD59-IRIS isoforms in human diabetic islets, showing a link between dysregulation of IRIS isoforms and defects in insulin secretion in diabetic patients. These data open a path for future studies into CD59-IRIS expression and function in additional cell types capable of regulated secretion. Identification of additional specific CD59-IRIS binding partners within the cell could provide therapeutic targets for enhancement of insulin secretion in T2D.

KW - Alternative Splicing

KW - CD59 Antigens/genetics

KW - Diabetes Mellitus/genetics

KW - Humans

KW - Insulin Secretion

KW - Protein Isoforms/genetics

U2 - 10.1073/pnas.2120083119

DO - 10.1073/pnas.2120083119

M3 - Article

C2 - 35666870

VL - 119

JO - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

SN - 1091-6490

IS - 24

ER -

Alternative splicing encodes functional intracellular CD59 isoforms that mediate insulin secretion and are down-regulated in diabetic islets

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