Next >  
ARTC1-mediated VAPB ADP-ribosylation regulates calcium homeostasis 
Xueyao Ma1,† , Mengyuan Li1,† , Yi Liu1,† , Xuefang Zhang1,† , Xiaoyun Yang1 , Yun Wang2 , Yipeng Li1 , Jiayue Wang1 , Xiuhua Liu1 , Zhenzhen Yan1,* , Xiaochun Yu3,4,5,* , Chen Wu1,*
1College of Life Sciences, Institute of Life Sciences and Green Development, Hebei University, Baoding 071002, China
2Department of Public Health, Affiliated Hospital of Hebei University, Baoding 071000, China
3Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, China
4School of Life Sciences, Westlake University, Hangzhou 310024, China
5Institute of Biology, Westlake Institute for Advanced Study, Hangzhou 310024, China
These authors contributed equally to this work.
*Correspondence to:Chen Wu , Xiaochun Yu , Zhenzhen Yan ,
J Mol Cell Biol, Volume 15, Issue 7, July 2023, mjad043,
Keyword: ATRCs, mono-ADP-ribosylation, hARTC1, VAPB, calcium homeostasis

Mono-ADP-ribosylation (MARylation) is a post-translational modification that regulates a variety of biological processes, including DNA damage repair, cell proliferation, metabolism, and stress and immune responses. In mammals, MARylation is mainly catalyzed by ADP-ribosyltransferases (ARTs), which consist of two groups: ART cholera toxin-like (ARTCs) and ART diphtheria toxin-like (ARTDs, also known as PARPs). The human ARTC (hARTC) family is composed of four members: two active mono-ADP-ARTs (hARTC1 and hARTC5) and two enzymatically inactive enzymes (hARTC3 and hARTC4). In this study, we systematically examined the homology, expression, and localization pattern of the hARTC family, with a particular focus on hARTC1. Our results showed that hARTC3 interacted with hARTC1 and promoted the enzymatic activity of hARTC1 by stabilizing hARTC1. We also identified vesicle-associated membrane protein-associated protein B (VAPB) as a new target of hARTC1 and pinpointed Arg50 of VAPB as the ADP-ribosylation site. Furthermore, we demonstrated that knockdown of hARTC1 impaired intracellular calcium homeostasis, highlighting the functional importance of hARTC1-mediated VAPB Arg50 ADP-ribosylation in regulating calcium homeostasis. In summary, our study identified a new target of hARTC1 in the endoplasmic reticulum and suggested that ARTC1 plays a role in regulating calcium signaling.