Arf GTPase-activating proteins SMAP1 and AGFG2 regulate the size of Weibel-Palade bodies and exocytosis of von Willebrand factor

Arf GTPase-Activating proteins (ArfGAPs) mediate the hydrolysis of GTP bound to ADP-ribosylation factors (Arfs), which are critical to form transport intermediates. ArfGAPs have been thought to be negative regulators of Arfs; however, accumulating evidence indicates that ArfGAPs are important for ca...

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Autores principales:	Asano Watanabe, Hikari Hataida, Naoya Inoue, Kosuke Kamon, Keigo Baba, Kuniaki Sasaki, Rika Kimura, Honoka Sasaki, Yuka Eura, Wei-Fen Ni, Yuji Shibasaki, Satoshi Waguri, Koichi Kokame, Yoko Shiba
Formato:	article
Lenguaje:	EN
Publicado:	The Company of Biologists 2021
Materias:	arf arfgap secretory granule exocytosis vwf wpb Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/37c4573f900a4b4b9c4c349226fa51b5
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spelling	oai:doaj.org-article:37c4573f900a4b4b9c4c349226fa51b52021-11-28T16:01:17ZArf GTPase-activating proteins SMAP1 and AGFG2 regulate the size of Weibel-Palade bodies and exocytosis of von Willebrand factor2046-639010.1242/bio.058789https://doaj.org/article/37c4573f900a4b4b9c4c349226fa51b52021-09-01T00:00:00Zhttp://bio.biologists.org/content/10/9/bio058789https://doaj.org/toc/2046-6390Arf GTPase-Activating proteins (ArfGAPs) mediate the hydrolysis of GTP bound to ADP-ribosylation factors (Arfs), which are critical to form transport intermediates. ArfGAPs have been thought to be negative regulators of Arfs; however, accumulating evidence indicates that ArfGAPs are important for cargo sorting and promote membrane traffic. Weibel-Palade bodies (WPBs) are cigar-shaped secretory granules in endothelial cells that contain von Willebrand factor (vWF) as their main cargo. WPB biogenesis at the Golgi was reported to be regulated by Arf and their regulators, but the role of ArfGAPs has been unknown. In this study, we performed siRNA screening of ArfGAPs to investigate the role of ArfGAPs in the biogenesis of WPBs. We found two ArfGAPs, SMAP1 and AGFG2, to be involved in WPB size and vWF exocytosis, respectively. SMAP1 depletion resulted in small-sized WPBs, and the lysosomal inhibitor leupeptin recovered the size of WPBs. The results indicate that SMAP1 functions in preventing the degradation of cigar-shaped WPBs. On the other hand, AGFG2 downregulation resulted in the inhibition of vWF secretion upon Phorbol 12-myristate 13-acetate (PMA) or histamine stimulation, suggesting that AGFG2 plays a role in vWF exocytosis. Our study revealed unexpected roles of ArfGAPs in vWF transport.Asano WatanabeHikari HataidaNaoya InoueKosuke KamonKeigo BabaKuniaki SasakiRika KimuraHonoka SasakiYuka EuraWei-Fen NiYuji ShibasakiSatoshi WaguriKoichi KokameYoko ShibaThe Company of Biologistsarticlearfarfgapsecretory granuleexocytosisvwfwpbScienceQBiology (General)QH301-705.5ENBiology Open, Vol 10, Iss 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	arf arfgap secretory granule exocytosis vwf wpb Science Q Biology (General) QH301-705.5
spellingShingle	arf arfgap secretory granule exocytosis vwf wpb Science Q Biology (General) QH301-705.5 Asano Watanabe Hikari Hataida Naoya Inoue Kosuke Kamon Keigo Baba Kuniaki Sasaki Rika Kimura Honoka Sasaki Yuka Eura Wei-Fen Ni Yuji Shibasaki Satoshi Waguri Koichi Kokame Yoko Shiba Arf GTPase-activating proteins SMAP1 and AGFG2 regulate the size of Weibel-Palade bodies and exocytosis of von Willebrand factor
description	Arf GTPase-Activating proteins (ArfGAPs) mediate the hydrolysis of GTP bound to ADP-ribosylation factors (Arfs), which are critical to form transport intermediates. ArfGAPs have been thought to be negative regulators of Arfs; however, accumulating evidence indicates that ArfGAPs are important for cargo sorting and promote membrane traffic. Weibel-Palade bodies (WPBs) are cigar-shaped secretory granules in endothelial cells that contain von Willebrand factor (vWF) as their main cargo. WPB biogenesis at the Golgi was reported to be regulated by Arf and their regulators, but the role of ArfGAPs has been unknown. In this study, we performed siRNA screening of ArfGAPs to investigate the role of ArfGAPs in the biogenesis of WPBs. We found two ArfGAPs, SMAP1 and AGFG2, to be involved in WPB size and vWF exocytosis, respectively. SMAP1 depletion resulted in small-sized WPBs, and the lysosomal inhibitor leupeptin recovered the size of WPBs. The results indicate that SMAP1 functions in preventing the degradation of cigar-shaped WPBs. On the other hand, AGFG2 downregulation resulted in the inhibition of vWF secretion upon Phorbol 12-myristate 13-acetate (PMA) or histamine stimulation, suggesting that AGFG2 plays a role in vWF exocytosis. Our study revealed unexpected roles of ArfGAPs in vWF transport.
format	article
author	Asano Watanabe Hikari Hataida Naoya Inoue Kosuke Kamon Keigo Baba Kuniaki Sasaki Rika Kimura Honoka Sasaki Yuka Eura Wei-Fen Ni Yuji Shibasaki Satoshi Waguri Koichi Kokame Yoko Shiba
author_facet	Asano Watanabe Hikari Hataida Naoya Inoue Kosuke Kamon Keigo Baba Kuniaki Sasaki Rika Kimura Honoka Sasaki Yuka Eura Wei-Fen Ni Yuji Shibasaki Satoshi Waguri Koichi Kokame Yoko Shiba
author_sort	Asano Watanabe
title	Arf GTPase-activating proteins SMAP1 and AGFG2 regulate the size of Weibel-Palade bodies and exocytosis of von Willebrand factor
title_short	Arf GTPase-activating proteins SMAP1 and AGFG2 regulate the size of Weibel-Palade bodies and exocytosis of von Willebrand factor
title_full	Arf GTPase-activating proteins SMAP1 and AGFG2 regulate the size of Weibel-Palade bodies and exocytosis of von Willebrand factor
title_fullStr	Arf GTPase-activating proteins SMAP1 and AGFG2 regulate the size of Weibel-Palade bodies and exocytosis of von Willebrand factor
title_full_unstemmed	Arf GTPase-activating proteins SMAP1 and AGFG2 regulate the size of Weibel-Palade bodies and exocytosis of von Willebrand factor
title_sort	arf gtpase-activating proteins smap1 and agfg2 regulate the size of weibel-palade bodies and exocytosis of von willebrand factor
publisher	The Company of Biologists
publishDate	2021
url	https://doaj.org/article/37c4573f900a4b4b9c4c349226fa51b5
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Arf GTPase-activating proteins SMAP1 and AGFG2 regulate the size of Weibel-Palade bodies and exocytosis of von Willebrand factor

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