title: CHHBP: a newly identified receptor of crustacean hyperglycemic hormone.
abstract: Crustacean hyperglycemic hormone (CHH) is a neurohormone found only in arthropods that plays a pivotal role in the regulation of hemolymph glucose levels, molting and stress responses. Although it was determined that a membrane guanylyl cyclase (GC) acts as the CHH receptor in the Y-organ during ecdysteroidogenesis, the identity of the CHH receptor in the hepatopancreas has not been established. In this study, we identified CHH binding protein (CHHBP), as a potential receptor by screening the annotated unigenes from the transcriptome of ITALIC! Eriocheir sinensis, after removal of the eyestalk. Analysis of the binding affinity between CHH and CHHBP provided direct evidence that CHH interacts with CHHBP in a specific binding mode. Subsequent analysis showed that CHHBP is expressed primarily in the hepatopancreas where it localizes to the cell membrane. In addition, real-time PCR analysis showed that ITALIC! CHHBPtranscript levels gradually increase in the hepatopancreas following eyestalk ablation. RNAi-mediated suppression of ITALIC! CHHBPexpression resulted in decreased glucose levels. Furthermore, the reduction of blood glucose induced by ITALIC! CHHBPRNAi reached the same level as that observed in the eyestalk ablation group, suggesting that CHHBP is involved in glucose metabolism regulated by CHH. In addition, compared with the control group, injection of CHH was unable to rescue the decreased glucose levels in ITALIC! CHHBPRNAi crabs. CHH induced transport of 2-NBDG to the outside of cells, with indispensable assistance from CHHBP. Taken together, these findings suggest that CHHBP acts as one type of the primary signal processor of CHH-mediated regulation of cellular glucose metabolism.
authors.affiliation: Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Science, Tianjin Normal University, Tianjin 300387, People's Republic of China.
authors.forename: Ran
authors.initials: R
authors.lastname: Li
authors.affiliation: Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Science, Tianjin Normal University, Tianjin 300387, People's Republic of China.
authors.forename: Jin-Ze
authors.initials: JZ
authors.lastname: Tian
authors.affiliation: Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Science, Tianjin Normal University, Tianjin 300387, People's Republic of China.
authors.forename: Cui-Heng
authors.initials: CH
authors.lastname: Zhuang
authors.affiliation: Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Science, Tianjin Normal University, Tianjin 300387, People's Republic of China.
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Zhang
authors.affiliation: Tianjin Center for Control and Prevention of Aquatic Animal Infectious Disease, Tianjin 300221, People's Republic of China.
authors.forename: Xu-Yun
authors.initials: XY
authors.lastname: Geng
authors.affiliation: Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Science, Tianjin Normal University, Tianjin 300387, People's Republic of China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Zhu
authors.affiliation: Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Science, Tianjin Normal University, Tianjin 300387, People's Republic of China Tianjin Center for Control and Prevention of Aquatic Animal Infectious Disease, Tianjin 300221, People's Republic of China jinshsun@163.com.
authors.forename: Jin-Sheng
authors.initials: JS
authors.lastname: Sun
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D060829:Arthropod Proteins / Q000378:metabolism*; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism; D003386:Brachyura / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000378:metabolism; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D043143:Hepatopancreas / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007447:Invertebrate Hormones / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D060829:Arthropod Proteins; D001786:Blood Glucose; D007447:Invertebrate Hormones; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C106354:flotillins; C015947:hyperglycemic hormone, crustacean; D003847:Deoxyglucose; D009327:4-Chloro-7-nitrobenzofurazan; C098340:2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose
keywords: Cell signaling; Cell surface receptor; Crustacean hyperglycemic hormone; Eriocheir sinensis; Glucose metabolism; Hormone receptor; Protein–protein interaction