ANKRD22 is an N-myristoylated hairpin-like monotopic membrane protein specifically localized to lipid droplets

Abstract The membrane topology and intracellular localization of ANKRD22, a novel human N-myristoylated protein with a predicted single-pass transmembrane domain that was recently reported to be overexpressed in cancer, were examined. Immunofluorescence staining of COS-1 cells transfected with cDNA...

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Autores principales:	Toshihiko Utsumi, Takuro Hosokawa, Mayu Shichita, Misato Nishiue, Natsuko Iwamoto, Haruna Harada, Aya Kiwado, Manami Yano, Motoaki Otsuka, Koko Moriya
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c686d4478e2547978727bd554bb80151
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spelling	oai:doaj.org-article:c686d4478e2547978727bd554bb801512021-12-02T19:16:47ZANKRD22 is an N-myristoylated hairpin-like monotopic membrane protein specifically localized to lipid droplets10.1038/s41598-021-98486-82045-2322https://doaj.org/article/c686d4478e2547978727bd554bb801512021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98486-8https://doaj.org/toc/2045-2322Abstract The membrane topology and intracellular localization of ANKRD22, a novel human N-myristoylated protein with a predicted single-pass transmembrane domain that was recently reported to be overexpressed in cancer, were examined. Immunofluorescence staining of COS-1 cells transfected with cDNA encoding ANKRD22 coupled with organelle markers revealed that ANKRD22 localized specifically to lipid droplets (LD). Analysis of the intracellular localization of ANKRD22 mutants C-terminally fused to glycosylatable tumor necrosis factor (GLCTNF) and assessment of their susceptibility to protein N-glycosylation revealed that ANKRD22 is synthesized on the endoplasmic reticulum (ER) membrane as an N-myristoylated hairpin-like monotopic membrane protein with the amino- and carboxyl termini facing the cytoplasm and then sorted to LD. Pro98 located at the center of the predicted membrane domain was found to be essential for the formation of the hairpin-like monotopic topology of ANKRD22. Moreover, the hairpin-like monotopic topology, and positively charged residues located near the C-terminus were demonstrated to be required for the sorting of ANKRD22 from ER to LD. Protein N-myristoylation was found to positively affect the LD localization. Thus, multiple factors, including hairpin-like monotopic membrane topology, C-terminal positively charged residues, and protein N-myristoylation cooperatively affected the intracellular targeting of ANKRD22 to LD.Toshihiko UtsumiTakuro HosokawaMayu ShichitaMisato NishiueNatsuko IwamotoHaruna HaradaAya KiwadoManami YanoMotoaki OtsukaKoko MoriyaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Toshihiko Utsumi Takuro Hosokawa Mayu Shichita Misato Nishiue Natsuko Iwamoto Haruna Harada Aya Kiwado Manami Yano Motoaki Otsuka Koko Moriya ANKRD22 is an N-myristoylated hairpin-like monotopic membrane protein specifically localized to lipid droplets
description	Abstract The membrane topology and intracellular localization of ANKRD22, a novel human N-myristoylated protein with a predicted single-pass transmembrane domain that was recently reported to be overexpressed in cancer, were examined. Immunofluorescence staining of COS-1 cells transfected with cDNA encoding ANKRD22 coupled with organelle markers revealed that ANKRD22 localized specifically to lipid droplets (LD). Analysis of the intracellular localization of ANKRD22 mutants C-terminally fused to glycosylatable tumor necrosis factor (GLCTNF) and assessment of their susceptibility to protein N-glycosylation revealed that ANKRD22 is synthesized on the endoplasmic reticulum (ER) membrane as an N-myristoylated hairpin-like monotopic membrane protein with the amino- and carboxyl termini facing the cytoplasm and then sorted to LD. Pro98 located at the center of the predicted membrane domain was found to be essential for the formation of the hairpin-like monotopic topology of ANKRD22. Moreover, the hairpin-like monotopic topology, and positively charged residues located near the C-terminus were demonstrated to be required for the sorting of ANKRD22 from ER to LD. Protein N-myristoylation was found to positively affect the LD localization. Thus, multiple factors, including hairpin-like monotopic membrane topology, C-terminal positively charged residues, and protein N-myristoylation cooperatively affected the intracellular targeting of ANKRD22 to LD.
format	article
author	Toshihiko Utsumi Takuro Hosokawa Mayu Shichita Misato Nishiue Natsuko Iwamoto Haruna Harada Aya Kiwado Manami Yano Motoaki Otsuka Koko Moriya
author_facet	Toshihiko Utsumi Takuro Hosokawa Mayu Shichita Misato Nishiue Natsuko Iwamoto Haruna Harada Aya Kiwado Manami Yano Motoaki Otsuka Koko Moriya
author_sort	Toshihiko Utsumi
title	ANKRD22 is an N-myristoylated hairpin-like monotopic membrane protein specifically localized to lipid droplets
title_short	ANKRD22 is an N-myristoylated hairpin-like monotopic membrane protein specifically localized to lipid droplets
title_full	ANKRD22 is an N-myristoylated hairpin-like monotopic membrane protein specifically localized to lipid droplets
title_fullStr	ANKRD22 is an N-myristoylated hairpin-like monotopic membrane protein specifically localized to lipid droplets
title_full_unstemmed	ANKRD22 is an N-myristoylated hairpin-like monotopic membrane protein specifically localized to lipid droplets
title_sort	ankrd22 is an n-myristoylated hairpin-like monotopic membrane protein specifically localized to lipid droplets
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c686d4478e2547978727bd554bb80151
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ANKRD22 is an N-myristoylated hairpin-like monotopic membrane protein specifically localized to lipid droplets

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