title: HECTD1 controls the protein level of IQGAP1 to regulate the dynamics of adhesive structures.
abstract: Cell migration including collective cell movement and individual cell migration are crucial factors in embryogenesis. During the spreading/migration of cells, several types of adhesive structures physically interacting with the extracellular matrix (ECM) or with another cell have been described and the formation and maturation of adhesion structures are coordinated, however the molecular pathways involved are still not fully understood.
  
  
  
  We generated a mouse embryonic fibroblast line (MEF) from homozygous mutant (Hectd1R/R, Hectd1Gt(RRC200)) mouse of the E3 ubiquitin ligase for inhibin B receptor (Hectd1). Detailed examination of cell motion on MEF cells demonstrated that loss of Hectd1 resulted in accelerated cell spreading and migration but impaired directionality of migration. In Hectd1R/Rcells paxillin and zyxin were largely mis-localized, whereas their expression levels were unchanged. In addition the formation of focal adhesions (FAs) was impaired and the focal complexes (FXs) were increased. We further identified HECTD1 as a key regulator of IQGAP1. IQGAP1 co-localized together with HECTD1 in the leading edge of cells. HECTD1 interacted with IQGAP1 and regulated its degradation through ubiquitination. Over-expression of IQGAP1 in control MEF phenocopied the spreading and migration defects of Hectd1R/Rcells. In contrast, siRNA-mediated knockdown of IQGAP1 rescued the defects in cellular movement of Hectd1R/Rcells.
  
  
  
  The E3 ligase activity of Hectd1 regulates the protein level of IQGAP1 through ubiquitination and therefore mediates the dynamics of FXs including the recruitment of paxillin and actinin. IQGAP1 is one of the effectors of HECTD1.
authors.affiliation: Department of Biomedicine, University Hospital, University of Basel, Basel, Switzerland.|Present Address: Chongqing Reproductive and Genetics Institute, 64 Jing Tang ST, Yu Zhong District, Chongqing, 400013, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Biomedicine, University Hospital, University of Basel, Basel, Switzerland.|Present Address: 2nd hospital of Jilin University, Changchun, China.
authors.forename: Zanhui
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Biomedicine, University Hospital, University of Basel, Basel, Switzerland.
authors.forename: Donato
authors.initials: D
authors.lastname: D'Alonzo
authors.affiliation: Department of Biomedicine, University Hospital, University of Basel, Basel, Switzerland.
authors.forename: Xinggang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Pathologie, Universitätsspital Basel, Schönbeinstrasse 40, CH-4031, Basel, Switzerland.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bruder
authors.affiliation: Clinic of Gynecological Endocrinology and Reproductive Medicine, University Hospital, University of Basel, Basel, Switzerland.
authors.forename: Fabienne Hélène
authors.initials: FH
authors.lastname: Emch
authors.affiliation: Department of Biomedicine, University Hospital, University of Basel, Basel, Switzerland.|Clinic of Gynecological Endocrinology and Reproductive Medicine, University Hospital, University of Basel, Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: De Geyter
authors.affiliation: Department of Biomedicine, University Hospital, University of Basel, Basel, Switzerland. hzhang@uhbs.ch.|Department of Biomedicine, University of Basel, Hebelstra. 20, CH-4031, Basel, Switzerland. hzhang@uhbs.ch.
authors.forename: Hong
authors.identifier: 0000-0002-7729-9202
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D051419:Paxillin / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D059008:Time-Lapse Imaging; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination; D060589:Zyxin / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000378:metabolism*
chemical_list: D005353:Fibronectins; D049452:Green Fluorescent Proteins; D051419:Paxillin; D034741:RNA, Small Interfering; D044767:Ubiquitin-Protein Ligases; D060589:Zyxin; D020703:ras GTPase-Activating Proteins; C101203:IQ motif containing GTPase activating protein 1; C000588989:HECTD1 protein, human; C521132:Hectd1 protein, mouse
keywords: Cell movement; Cell spreading; Focal adhesions; HECTD1; IQGAP1; Ubiquitination