title: The nuclear envelope protein Nesprin-2 has roles in cell proliferation and differentiation during wound healing.
abstract: Nesprin-2, a type II transmembrane protein of the nuclear envelope, is a component of the LINC complex that connects the nuclear lamina with the actin cytoskeleton. To elucidate its physiological role we studied wound healing in Nesprin-2 Giant deficient mice and found that a loss of the protein affected wound healing particularly at later stages during fibroblast differentiation and keratinocyte proliferation leading to delayed wound closure. We identified altered expression and localization of transcription factors as one of the underlying mechanisms. Furthermore, the actin cytoskeleton which surrounds the nucleus was altered and keratinocyte migration was slowed down and focal adhesion formation enhanced. We also uncovered a new activity of Nesprin-2. When we probed for an interaction of Nesprin-2 Giant with chromatin we observed in ChIP Seq experiments an association of the protein with heterochromatic and centromeric DNA. Through this activity Nesprin-2 can affect the nuclear landscape and gene regulation. Our findings suggest functions for Nesprin-2 at the nuclear envelope (NE) in gene regulation and in regulation of the actin cytoskeleton which impact on wound healing.
authors.affiliation: Institute of Biochemistry I, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: R N
authors.initials: RN
authors.lastname: Rashmi
authors.forename: Beate
authors.initials: B
authors.lastname: Eckes
authors.forename: Gernot
authors.initials: G
authors.lastname: Glöckner
authors.forename: Marco
authors.initials: M
authors.lastname: Groth
authors.forename: Sascha
authors.initials: S
authors.lastname: Neumann
authors.forename: Joachim
authors.initials: J
authors.lastname: Gloy
authors.forename: Lorenz
authors.initials: L
authors.lastname: Sellin
authors.forename: Gerd
authors.initials: G
authors.lastname: Walz
authors.forename: Maria
authors.initials: M
authors.lastname: Schneider
authors.forename: Iakowos
authors.initials: I
authors.lastname: Karakesisoglou
authors.forename: Ludwig
authors.initials: L
authors.lastname: Eichinger
authors.forename: Angelika A
authors.initials: AA
authors.lastname: Noegel
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D022001:Focal Adhesions / Q000187:drug effects; D055786:Gene Knockout Techniques; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects
chemical_list: D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016760:Proto-Oncogene Proteins c-fos; D051785:Smad Proteins; C485903:Syne2 protein, mouse; D016212:Transforming Growth Factor beta