HGNC Approved Gene Symbol: ZYX
Cytogenetic location: 7q34 Genomic coordinates (GRCh38): 7:143,381,345-143,391,111 (from NCBI)
Zyxin, a member of the LIM protein family (see 600824), is an adapter protein present in focal adhesions in eukaryotic cells that plays a role in regulation of the organization of the actin cytoskeleton (summary by Li et al., 2004).
Macalma et al. (1996) stated that zyxin is a phosphoprotein concentrated at adhesion plaques and along actin filament bundles near where they insert at the adhesion plaques. Macalma et al. (1996) cloned mouse and human cDNAs encoding zyxin. The human gene encodes a 572-amino acid polypeptide with a predicted unmodified molecular weight of 61 kD. The polypeptide sequence displayed 58% identity to chicken zyxin, having a proline-rich N-terminal region and 3 tandemly arranged LIM domains in the C-terminal region. Macalma et al. (1996) stated that the proline-rich region is likely to interact with SH3 domains that are linked to signal transduction pathways, while LIM domains are known protein-protein binding regions that are found in a number of proteins involved in regulation of cell proliferation and differentiation. Northern blot analysis revealed that the 2.2-kb human zyxin transcript is ubiquitously expressed. Macalma et al. (1996) used immunofluorescence to localize human zyxin to the focal contacts of adherent HEL cells. Southern blot analysis revealed a hybridization pattern characteristic of that seen in single-copy genes.
By performing a yeast 2-hybrid screen of a HeLa cDNA library with LATS1 (603473) lacking its kinase region as bait, Hirota et al. (2000) isolated clones encoding ZYX. Immunoblot analysis confirmed that the 82-kD ZYX protein interacts through its C-terminal LIM1 and LIM2 domains with LATS1 in intact cells. Immunocytochemical analysis showed that ZYX is concentrated at focal adhesion plaques with bundles of actin filaments. In mitotic cells, however, ZYX is distributed diffusely in the cytoplasm, with a concentration in the mitotic apparatus, particularly in the spindle. The authors found that ZYX is phosphorylated in its N-terminal region by CDC2 kinase (116940), and this phosphorylation regulates its colocalization with LATS1. Expression of truncated LATS1 perturbed ZYX interaction with the mitotic apparatus and resulted in a prolongation of mitosis.
By yeast 2-hybrid and truncation analyses, Li et al. (2004) found that the C-terminal SH3 domain of LIM-nebulette (605491) interacted with an N-terminal motif of zyxin. Protein pull-down assays confirmed direct interaction between zyxin and both full-length LIM-nebulette and its isolated SH3 domain. The zyxin motif also interacted with the C-terminal SH3 domains of LASP1 (602920) and nebulin (NEB; 161650), but not with the SH3 domains of other proteins examined. Zyxin, LIM-nebulette, and LASP1 colocalized at focal adhesions in transfected HeLa and HT1080 cells.
Kanchanawong et al. (2010) used 3-dimensional super-resolution fluorescence microscopy to map nanoscale protein organization in focal adhesions. Their results revealed that integrins and actin are vertically separated by an approximately 40-nm focal adhesion core region consisting of multiple protein-specific strata: a membrane-apposed integrin signaling layer containing integrin cytoplasmic tails (see 193210), focal adhesion kinase (600758), and paxillin (602505); an intermediate force-transduction layer containing talin (186745) and vinculin (193065); and an uppermost actin-regulatory layer containing zyxin, vasodilator-stimulated phosphoprotein (601703), and alpha-actinin (102575). By localizing amino- and carboxy-terminally tagged talins, Kanchanawong et al. (2010) revealed talin's polarized orientation, indicative of a role in organizing the focal adhesion strata. Kanchanawong et al. (2010) concluded that their composite multilaminar protein architecture provided a molecular blueprint for understanding focal adhesion functions.
Macalma et al. (1996) used Southern blotting and PCR to map the zyxin gene to human chromosome 7q32-q36. By fluorescence in situ hybridization, Zumbrunn and Trueb (1998) refined the localization to 7q34-q35.
Hoffman et al. (2003) determined that Zyx knockout mice were viable and fertile, and they displayed no obvious histologic abnormalities in any of the organs examined. The authors noted that zyxin contributes to the subcellular localization of VASP (601703), but they were unable to identify defects of VASP mislocalization. Hoffman et al. (2003) concluded that other zyxin family members could have overlapping function and compensate for the loss of Zyx in the Zyx null mice.
Hirota, T., Morisaki, T., Nishiyama, Y., Marumoto, T., Tada, K., Hara, T., Masuko, N., Inagaki, M., Hatakeyama, K., Saya, H. Zyxin, a regulator of actin filament assembly, targets the mitotic apparatus by interacting with h-warts/LATS1 tumor suppressor. J. Cell Biol. 149: 1073-1086, 2000. [PubMed: 10831611] [Full Text: https://doi.org/10.1083/jcb.149.5.1073]
Hoffman, L. M., Nix, D. A., Benson, B., Boot-Hanford, R., Gustafsson, E., Jamora, C., Menzies, A. S., Goh, K. L., Jensen, C. C., Gertler, F. B., Fuchs, E., Fassler, R., Beckerle, M. C. Targeted disruption of the murine zyxin gene. Molec. Cell. Biol. 23: 70-79, 2003. [PubMed: 12482962] [Full Text: https://doi.org/10.1128/MCB.23.1.70-79.2003]
Kanchanawong, P., Shtengel, G., Pasapera, A. M., Ramko, E. B., Davidson, M. W., Hess, H. F., Waterman, C. M. Nanoscale architecture of integrin-based cell adhesions. Nature 468: 580-584, 2010. [PubMed: 21107430] [Full Text: https://doi.org/10.1038/nature09621]
Li, B., Zhuang, L., Trueb, B. Zyxin interacts with the SH3 domains of the cytoskeletal proteins LIM-nebulette and Lasp-1. J. Biol. Chem. 279: 20401-20410, 2004. [PubMed: 15004028] [Full Text: https://doi.org/10.1074/jbc.M310304200]
Macalma, T., Otte, J., Hensler, M. E., Bockholt, S. M., Louis, H. A., Kalff-Suske, M., Grzeschik, K.-H., von der Ahe, D., Beckerle, M. C. Molecular characterization of human zyxin. J. Biol. Chem. 271: 31470-31478, 1996. [PubMed: 8940160] [Full Text: https://doi.org/10.1074/jbc.271.49.31470]
Zumbrunn, J., Trueb, B. Assignment of the ZYX gene for the LIM protein zyxin to human chromosome bands 7q34-q35 by in situ hybridization. Cytogenet. Cell Genet. 81: 283-284, 1998. [PubMed: 9730620] [Full Text: https://doi.org/10.1159/000015047]