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The nuclear envelope protein Nesprin-2 has roles in cell proliferation and differentiation during wound healing.

Rashmi RN, Eckes B, Glöckner G, Groth M, Neumann S, Gloy J, Sellin L, Walz G, Schneider M, Karakesisoglou I, Eichinger L, Noegel AA - Nucleus (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biochemistry I, Medical Faculty, University of Cologne, Cologne, Germany.

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.

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Nesprin-2 mediates the translocation of c-Fos after TGFβ induction. (A) Nuclear translocation of transcription factor c-Fos was studied in control and KD HaCaT cells after induction with TGFβ. Scale bar, 25 µm. (B) Statistical analysis of the percentage of cells showing nuclear localization of c-Fos.
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Figure 8: Nesprin-2 mediates the translocation of c-Fos after TGFβ induction. (A) Nuclear translocation of transcription factor c-Fos was studied in control and KD HaCaT cells after induction with TGFβ. Scale bar, 25 µm. (B) Statistical analysis of the percentage of cells showing nuclear localization of c-Fos.

Mentions: We obtained similar results for c-Fos, a subunit of the AP1 transcription factor. In control cells 10 min after TGFβ stimulation strong nuclear staining was observed whereas KD cells showed a comparable staining only after 20 min (Fig. 8A and B). The analysis of wounded tissue was prevented as c-Fos antibodies did not work reliably for staining of skin sections.


The nuclear envelope protein Nesprin-2 has roles in cell proliferation and differentiation during wound healing.

Rashmi RN, Eckes B, Glöckner G, Groth M, Neumann S, Gloy J, Sellin L, Walz G, Schneider M, Karakesisoglou I, Eichinger L, Noegel AA - Nucleus (2012)

Nesprin-2 mediates the translocation of c-Fos after TGFβ induction. (A) Nuclear translocation of transcription factor c-Fos was studied in control and KD HaCaT cells after induction with TGFβ. Scale bar, 25 µm. (B) Statistical analysis of the percentage of cells showing nuclear localization of c-Fos.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3383573&req=5

Figure 8: Nesprin-2 mediates the translocation of c-Fos after TGFβ induction. (A) Nuclear translocation of transcription factor c-Fos was studied in control and KD HaCaT cells after induction with TGFβ. Scale bar, 25 µm. (B) Statistical analysis of the percentage of cells showing nuclear localization of c-Fos.
Mentions: We obtained similar results for c-Fos, a subunit of the AP1 transcription factor. In control cells 10 min after TGFβ stimulation strong nuclear staining was observed whereas KD cells showed a comparable staining only after 20 min (Fig. 8A and B). The analysis of wounded tissue was prevented as c-Fos antibodies did not work reliably for staining of skin sections.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biochemistry I, Medical Faculty, University of Cologne, Cologne, Germany.

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.

Show MeSH
Related in: MedlinePlus