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
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.[1] [2] [3] [4]
Publication Abstract from PubMed
The nuclear position in eukaryotes is controlled by a nucleo-cytoskeletal network, critical in cell differentiation, division, and movement. Forces are transmitted through conserved Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes that traverse the nuclear envelope and engage on either side of the membrane with diverse binding partners. Nesprin-2-giant (Nes2G), a LINC element in the outer nuclear membrane, connects to the actin directly as well as through FHOD1, a formin primarily involved in actin bundling. Here, we report the crystal structure of Nes2G bound to FHOD1 and show that the presumed G-binding domain of FHOD1 is rather a spectrin repeat (SR) binding enhancer for the neighboring FH3 domain. The structure reveals that SR binding by FHOD1 is likely not regulated by the diaphanous-autoregulatory domain helix of FHOD1. Finally, we establish that Nes1G also has one FHOD1 binding SR, indicating that these abundant, giant Nesprins have overlapping functions in actin-bundle recruitment for nuclear movement.
Structures of FHOD1-Nesprin1/2 complexes reveal alternate binding modes for the FH3 domain of formins.,Lim SM, Cruz VE, Antoku S, Gundersen GG, Schwartz TU Structure. 2021 Jun 3;29(6):540-552.e5. doi: 10.1016/j.str.2020.12.013. Epub 2021 , Jan 19. PMID:33472039[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Lim SM, Cruz VE, Antoku S, Gundersen GG, Schwartz TU. Structures of FHOD1-Nesprin1/2 complexes reveal alternate binding modes for the FH3 domain of formins. Structure. 2021 Jun 3;29(6):540-552.e5. PMID:33472039 doi:10.1016/j.str.2020.12.013
