4dxs

Structural highlights

Disease

[SYNE2_HUMAN] Autosomal dominant Emery-Dreifuss muscular dystrophy. The disease is caused by mutations affecting the gene represented in this entry.

Function

[SUN2_HUMAN] Component of SUN-protein-containing multivariate complexes also called LINC complexes which link the nucleoskeleton and cytoskeleton by providing versatile outer nuclear membrane attachment sites for cytoskeletal filaments. Specifically, SYNE2 and SUN2 assemble in arrays of transmembrane actin-associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow during actin-dependent nuclear movement. Required for interkinetic nuclear migration (INM) and essential for nucleokinesis and centrosome-nucleus coupling during radial neuronal migration in the cerebral cortex and during glial migration. Anchors chromosome movement in the prophase of meiosis and is involved in selective gene expression of coding and non-coding RNAs needed for gametogenesis. Required for telomere attachment to nuclear envelope and gametogenesis. May also function on endocytic vesicles as a receptor for RAB5-GDP and participate in the activation of RAB5.^[1] [SYNE2_HUMAN] Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. Component of SUN-protein-containing multivariate complexes also called LINC complexes which link the nucleoskeleton and cytoskeleton by providing versatile outer nuclear membrane attachment sites for cytoskeletal filaments. Involved in the maintenance of nuclear organization and structural integrity. Connects nuclei to the cytoskeleton by interacting with the nuclear envelope and with F-actin in the cytoplasm. Specifically, SYNE2 and SUN2 assemble in arrays of transmembrane actin-associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow during actin-dependent nuclear movement. Required for centrosome migration to the apical cell surface during early ciliogenesis.^{[2] [3] [4] [5]}

References

1. ↑ Stewart-Hutchinson PJ, Hale CM, Wirtz D, Hodzic D. Structural requirements for the assembly of LINC complexes and their function in cellular mechanical stiffness. Exp Cell Res. 2008 May 1;314(8):1892-905. doi: 10.1016/j.yexcr.2008.02.022. Epub , 2008 Mar 12. PMID:18396275 doi:http://dx.doi.org/10.1016/j.yexcr.2008.02.022
2. ↑ Zhen YY, Libotte T, Munck M, Noegel AA, Korenbaum E. NUANCE, a giant protein connecting the nucleus and actin cytoskeleton. J Cell Sci. 2002 Aug 1;115(Pt 15):3207-22. PMID:12118075
3. ↑ Stewart-Hutchinson PJ, Hale CM, Wirtz D, Hodzic D. Structural requirements for the assembly of LINC complexes and their function in cellular mechanical stiffness. Exp Cell Res. 2008 May 1;314(8):1892-905. doi: 10.1016/j.yexcr.2008.02.022. Epub , 2008 Mar 12. PMID:18396275 doi:http://dx.doi.org/10.1016/j.yexcr.2008.02.022
4. ↑ Dawe HR, Adams M, Wheway G, Szymanska K, Logan CV, Noegel AA, Gull K, Johnson CA. Nesprin-2 interacts with meckelin and mediates ciliogenesis via remodelling of the actin cytoskeleton. J Cell Sci. 2009 Aug 1;122(Pt 15):2716-26. doi: 10.1242/jcs.043794. Epub 2009 Jul, 13. PMID:19596800 doi:http://dx.doi.org/10.1242/jcs.043794
5. ↑ Luxton GW, Gomes ER, Folker ES, Vintinner E, Gundersen GG. Linear arrays of nuclear envelope proteins harness retrograde actin flow for nuclear movement. Science. 2010 Aug 20;329(5994):956-9. doi: 10.1126/science.1189072. PMID:20724637 doi:http://dx.doi.org/10.1126/science.1189072
6. ↑ Sosa BA, Rothballer A, Kutay U, Schwartz TU. LINC Complexes Form by Binding of Three KASH Peptides to Domain Interfaces of Trimeric SUN Proteins. Cell. 2012 May 25;149(5):1035-47. PMID:22632968 doi:10.1016/j.cell.2012.03.046