2026-03-06T03:33:49Z https://iwate-u.repo.nii.ac.jp/oai

oai:iwate-u.repo.nii.ac.jp:00015786 2025-09-29T05:56:51Z 1515:1519

Arf GTPase-activating proteins SMAP1 and AGFG2 regulate the size of Weibel-Palade bodies and exocytosis of von Willebrand factor WATANABE, Asano Iwate University HATAIDA, Hikari Iwate University INOUE, Naoya Iwate University KAMON, Kosuke Iwate Univeresity BABA, Keigo Iwate University SASAKI, Kuniaki Iwate University KIMURA, Rika Iwate University SASAKI, Honoka Iwate University EURA, Yuka National Cerebral and Cardiovascular Center NI, Wei-Fen National Kaohsiung Normal University SHIBASAKI, Yuji Iwate University WAGURI, Satoshi Fukushima Medical University KOKAME, Koichi National Cerebral and Cardiovascular Center SHIBA, Yoko Iwate University open access Creative Commons Attribution 4.0 International Arf ArfGAP Secretory granule Exocytosis VWF WPB 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. The Company of Biologists Ltd 2021-09-01 eng journal article VoR https://iwate-u.repo.nii.ac.jp/records/15786 https://doi.org/10.1242/bio.058789 2046-6390 Biology Open 10 9 bio058789 https://iwate-u.repo.nii.ac.jp/record/15786/files/bo-v10n9pbio058789.pdf application/pdf 6.9MB 2022-09-12