GPCR/endocytosis/ERK signaling/S2R is involved in the regulation of the internalization,mitochondria-targeting and-activating properties of human salivary histatin 1

作     者：Dandan Ma Wei Sun Cuicui Fu Kamran Nazmi Enno C.I.Veerman Richard T.Jaspers Jan G.M.Bolscher Floris J.Bikker Gang Wu Dandan Ma;Wei Sun;Cuicui Fu;Kamran Nazmi;Enno C. I. Veerman;Richard T. Jaspers;Jan G. M. Bolscher;Floris J. Bikker;Gang Wu

作者机构：Department of Oral BiochemistryAcademic Centre for Dentistry Amsterdam(ACTA)University of Amsterdam and Vrije Universiteit AmsterdamAmsterdamNetherlands School of StomatologyZhejiang Chinese Medical UniversityHangzhouChina Laboratory for MyologyDepartment of Human Movement SciencesFaculty of Behavioral and Movement SciencesAmsterdam Movement SciencesVrije Universiteit AmsterdamAmsterdamNetherlands Department of Oral Cell BiologyAcademic Centre for Dentistry Amsterdam(ACTA)University of Amsterdam and Vrije Universiteit AmsterdamAmsterdamNetherlands Department of Oral and Maxillofacial Surgery/PathologyAmsterdam UMC and Academic Center for Dentistry Amsterdam(ACTA)Vrije Universiteit AmsterdamAmsterdam Movement ScienceAmsterdamNetherlands 

出 版 物：《International Journal of Oral Science》 (国际口腔科学杂志（英文版）)

年 卷 期：2022年第14卷第3期

页      面：334-348页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 100101[医学-人体解剖与组织胚胎学] 10[医学] 

基　　金：funded by Eurostars project grant number E!12764 

主　　题：GPCR/endocytosis/ERK signaling/S2R is involved in the regulation of the internalization mitochondria-targeting and activating properties of human salivary histatin 1 ERK 

摘      要：Human salivary histatin 1(Hst1)exhibits a series of cell-activating properties,such as promoting cell spreading,migration,and metabolic *** recently have shown that fluorescently labeled Hst1(F-Hst1)targets and activates mitochondria,presenting an important molecular ***,its regulating signaling pathways remain to be *** investigated the influence of specific inhibitors of G protein-coupled receptors(GPCR),endocytosis pathways,extracellular signal-regulated kinases1/2(ERK1/2)signaling,p38 signaling,mitochondrial respiration and Na+/K+-ATPase activity on the uptake,mitochondria-targeting and-activating properties of *** performed a si RNA knockdown(KD)to assess the effect of Sigma-2 receptor(S2R)/Transmembrane Protein 97(TMEM97)—a recently identified target protein of *** also adopted live cell imaging to monitor the whole intracellular trafficking process of *** results showed that the inhibition of cellular respiration hindered the internalization of *** inhibitors of GPCR,ERK1/2,phagocytosis,and clathrin-mediated endocytosis(CME)as well as siRNA KD of S2R/TMEM97 significantly reduced the uptake,which was accompanied by the nullification of the promoting effect of F-Hst1 on cell metabolic *** the inhibitor of CME and KD of S2R/TMEM97 significantly compromised the mitochondria-targeting of *** further showed the intracellular trafficking and targeting process of F-Hst1,in which early endosome plays an important ***,phagocytosis,CME,GPCR,ERK signaling,and S2R/TMEM97 are involved in the internalization of Hst1,while only CME and S2R/TMEM97 are critical for its subcellular *** inhibition of either internalization or mitochondria-targeting of Hst1 could significantly compromise its mitochondria-activating property.