Nesprin

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Nuclear localization of the Nesprin2 protein in COS-7 cells . (A) Nesprin2 staining by pAb K1 (secondary antibody α-rabbit TRITC conjugate), (B) actin staining by FITC -phalloidin, (C) Lamin A / C staining by monoclonal α-Lamin A / C antibody (JOL2) (secondary Antibody α-mouse Cy5 conjugate). The cells were fixed with 3% PFA and permeabilized with 0.5% Triton X-100. The images were taken with the confocal laser scanning microscope. Bar 25 µm

The Nesprins (English for N uclear E nvelope SP ect RIN repeat) are a family of proteins , primarily in the outer nuclear membrane can be found. Nesprin-1 (historical synonyms: Enaptin, Myne-1, Syne-1) and Nesprin-2 (historical synonyms: Nuance, Syne-2) have been described as actin- binding proteins of the α-actinin type.

Other research groups mainly examined C-terminal isoforms of Nesprin-1 and Nesprin-2. They showed that the conserved C-terminal region with the transmembrane domain is responsible for the localization in the inner nuclear membrane and that lamin A / C co-immunoprecipitates. Direct binding of Nesprin-1 to Lamin A and Emerin was later confirmed in vitro . Nesprin-1 isoforms have been shown to be able to interact with themselves or with the Golgi apparatus .

Nesprin-1 and Nesprin-2 have orthologous proteins in the slime mold Dictyostelium discoideum (Interaptin), in the fruit fly Drosophila melanogaster (MSP300) and the nematode Caenorhabditis elegans (ANC1). Mutations in ANC1 affect the localization of cell nuclei and mitochondria in C. elegans . ANC1 is a protein whose own nuclear localization depends on UNC84 and Ce-Lamin. As with Emerin, genetic defects in this protein family can lead to Emery Dreifuss muscular dystrophy .

The active positioning of the cell nucleus is an essential function in cell division, migration and differentiation of mammalian cells. During the migration of fibroblasts, the movement of the cell nucleus is dependent on N2G (Nesprin-2 Gigant). N2G is a large actin-binding protein in the outer nuclear envelope. It interacts with FHOD1 in binding strands of actin to the nuclear envelope. N2G-FHOD1 creates a stable connection between the nucleus and the contractile actin strands, which is necessary for movement.

Individual evidence

  1. ↑ S. Braune: Identification and characterization of enaptin, a new protein of the α-actinin type . Dissertation . University of Cologne, 2001.
  2. ↑ Y.-Y. Zhen: Identification and characterization of NUANCE, a new protein of the α – actinin type . Dissertation. University of Cologne, 2001.
  3. ^ YY Zhen, T. Libotte, M. Munck, AA Noegel, E. Korenbaum: NUANCE, a giant protein connecting the nucleus and actin cytoskeleton . In: J Cell Sci . tape 115 , August 2002, p. 3207-3222 , PMID 12118075 .
  4. ↑ JM Mislow, MS Kim, DB Davis, EM McNally: Myne-1, a spectrin repeat transmembrane protein of the inner nuclear membrane myocyte, inter acts with lamin A / C . In: J Cell Sci . tape 115 , January 2002, p. 61-70 , PMID 11801724 .
  5. ↑ JM Mislow, JM Holaska, MS Kim, KK Lee, M. Segura-Totten, KL Wilson, EM McNally: Nesprin-1alpha self-associates and binds directly to emerin and lamin A in vitro . In: FEBS Lett . tape 525 , no. 1-3 , August 2002, pp. 135-140 , PMID 12163176 .
  6. ↑ Q. Zhang, JN Skepper, F. Yang, JD Davies, L. Hegyi, RG Roberts, PL Weissberg, JA Ellis, CM Shanahan: Nesprins: a novel family of spectrin-repeat-containing proteins that localize to the nuclear membrane in multiple tissues . In: J Cell Sci . tape 114 , December 2001, p. 4485-4498 , PMID 11792814 .
  7. ↑ LL Gough, J. Fan, S. Chu, S. Winnick, KA Beck: Golgi localization of Syne-1 . In: Mol Biol Cell . tape 14 , no. 6 , June 2003, p. 2410-2424 , PMID 12808039 .
  8. ↑ Q. Zhang, C. Ragnauth, MJ Greener, CM Shanahan, RG Roberts: The nesprins are giant actin-binding proteins, orthologous to Drosophila melanogaster muscle protein MSP-300 . In: Genomics . tape 80 , no. 5 , November 2002, pp. 473-481 , PMID 12408964 .
  9. ↑ DA Starr, M. Han: Role of ANC-1 in tethering nuclei to the actin cytoskeleton . In: Science . tape 298 , no. 5592 , October 2002, p. 406-409 , PMID 12169658 .
  10. ↑ CJ Malone, WD Fixsen, HR Horvitz, M. Han: UNC-84 localizes to the nuclear envelope and is required for nuclear migration and anchoring during C. elegans development . In: Development . tape 126 , no. June 14 , 1999, p. 3171-3181 , PMID 10375507 .
  11. ↑ KK Lee, D. Starr, M. Cohen, J. Liu, M. Han, KL Wilson, Y. Gruenbaum: Lamin-dependent localization of UNC-84, a protein required for nuclear migration in Caenorhabditis elegans . In: Mol Biol Cell . tape 13 , no. 3 , March 2002, p. 892-901 , PMID 11907270 .
  12. ↑ J. Zhang et al: Nesprin 1 is critical for nuclear positioning and anchorage . In: Hum Mol Genet . tape 19 , no. 2 , January 2010, p. 329-341 , PMID 19864491 .
  13. ^ Gregg G. Gundersen, Oliver T. Fackler, Igor Stagljar, GW Gant Luxton, Susumu Antoku: FHOD1 interaction with nesprin-2G mediates TAN line formation and nuclear movement . In: Nature Cell Biology . tape 16 , no. 7 , 2014, ISSN  1476-4679 , p. 708-715 , doi : 10.1038 / ncb2981 , PMID 24880667 , PMC 4113092 (free full text).