ARTC1-mediated VAPB ADP-ribosylation regulates calcium homeostasis  

作　　者：Xueyao Ma Mengyuan Li Yi Liu Xuefang Zhang Xiaoyun Yang Yun Wang Yipeng Li Jiayue Wang Xiuhua Liu Zhenzhen Yan Xiaochun Yu Chen Wu 

机构地区：[1]College of Life Sciences,Institute of Life Sciences and Green Development,Hebei University,Baoding 071002,China [2]Department of Public Health,Affiliated Hospital of Hebei University,Baoding 071000,China [3]Westlake Laboratory of Life Sciences and Biomedicine,Hangzhou 310024,China [4]School of Life Sciences,Westlake University,Hangzhou 310024,China [5]Institute of Biology,Westlake Institute for Advanced Study,Hangzhou 310024,China

出　　处：《Journal of Molecular Cell Biology》2023年第7期1-14,共14页分子细胞生物学报（英文版）

基　　金：This work was supported by grants from the National Natural Science Foundation of China(32071277,82002594,81874160,and 32171295);the Natural Science Foundation of Hebei Province(C2021201012);S&T Program of Hebei(216Z2602G);the Interdisciplinary Research Program of Natural Science of Hebei University(DXK202006 and DXK202007);Hebei Natural Science Foundation for Outstanding Young Scholars(H2020201017);the High-level Talents Research Start-up Project of Hebei University(521000981352).

摘　　要：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.

关 键 词：ATRCs mono-ADP-ribosylation hARTC1 VAPB calcium homeostasis 

分 类 号：O64[理学—物理化学]