{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:44:32Z","timestamp":1790775872458,"version":"4.1.0"},"reference-count":43,"publisher":"The Company of Biologists","issue":"22","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,11,15]]},"abstract":"<jats:p>Plakins are a family of giant cytoskeleton binding proteins. One member of this group is bullous pemphigoid antigen 1 (Bpag1)\/dystonin, which has neuronal and muscle isoforms that consist of actin-binding and microtubule-binding domains at either end separated by a plakin domain and several spectrin repeats. The better-characterized epithelial isoform has only the plakin domain in common with the neuronal and muscle isoforms. Here, we have analyzed the localization of muscle\/neuronal (Bpag1a\/b) isoforms and the epithelial (Bpag1e) isoform within C2C12 myoblast cells. Although an antibody specific to Bpag1a\/b isoform 2 detected protein co-aligning actin stress fibers, this same antibody and two Bpag1e antibodies predominantly detected protein in the nuclei. A Bpag1a\/b isoform 2 N-terminal fusion protein containing the plakin domain also localized to actin stress fibers and to nuclei. Within the plakin domain, we characterized a functional nuclear localization signal, which was responsible for localization of the fusion protein to the nucleus. Bpag1a\/b isoform 1 N-terminal fusion proteins differed in their interaction with the actin cytoskeleton and with their ability to localize to the nucleus, suggesting that Bpag1 isoforms with different N-termini have differing roles. These results show the importance of N-terminal domains in dictating the localization and function of Bpag1 isoforms. We provide the first indication that Bpag1 is not strictly a cytoplasmic\/membrane protein but that it can also localize to the nucleus.<\/jats:p>","DOI":"10.1242\/jcs.00764","type":"journal-article","created":{"date-parts":[[2003,10,23]],"date-time":"2003-10-23T02:36:37Z","timestamp":1066876597000},"page":"4543-4555","source":"Crossref","is-referenced-by-count":44,"title":["Bpag1 localization to actin filaments and to the nucleus is regulated by its N-terminus"],"prefix":"10.1242","volume":"116","author":[{"given":"Kevin G.","family":"Young","sequence":"first","affiliation":[{"name":"Ottawa Health Research Institute, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6 The University of Ottawa Center for Neuromuscular Disease, Ottawa, Ontario, Canada K1H 8M5 Department of Cellular and Molecular Medicine, and Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline","family":"Pool","sequence":"additional","affiliation":[{"name":"Ottawa Health Research Institute, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6 The University of Ottawa Center for Neuromuscular Disease, Ottawa, Ontario, Canada K1H 8M5 Department of Cellular and Molecular Medicine, and Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashmi","family":"Kothary","sequence":"additional","affiliation":[{"name":"Ottawa Health Research Institute, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6 The University of Ottawa Center for Neuromuscular Disease, Ottawa, Ontario, Canada K1H 8M5 Department of Cellular and Molecular Medicine, and Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042517480795600_REF1","doi-asserted-by":"crossref","unstructured":"Andra, K., Nikolic, B., Stocher, M., Drenckhahn, D. and Wiche, G. (1998). Not just scaffolding: plectin regulates actin dynamics in cultured cells. Genes Dev.12, 3442-3451.","DOI":"10.1101\/gad.12.21.3442"},{"key":"2021042517480795600_REF2","doi-asserted-by":"crossref","unstructured":"Andra, K., Kornacker, I., Jorgl, A., Zorer, M., Spazierer, D., Fuchs, P., Fischer, I. and Wiche, G. (2003). Plectin-isoform-specific rescue of hemidesmosomal defects in plectin (\u2013\/\u2013) keratinocytes. J. Invest. Dermatol.120, 189-197.","DOI":"10.1046\/j.1523-1747.2003.12027.x"},{"key":"2021042517480795600_REF3","doi-asserted-by":"crossref","unstructured":"Bernier, G. and Kothary, R. (1998). Prenatal onset of axonopathy in Dystonia musculorum mice. Dev. Genet.22, 160-168.","DOI":"10.1002\/(SICI)1520-6408(1998)22:2<160::AID-DVG5>3.0.CO;2-4"},{"key":"2021042517480795600_REF4","doi-asserted-by":"crossref","unstructured":"Bernier, G., Brown, A., Dalpe\u0301, G., de Repentigny, Y., Mathieu, M. and Kothary, R. (1995). Dystonin expression in the developing nervous system predominates in the neurons that degenerate in dystonia musculorum mutant mice. Mol. Cell. Neurosci.6, 509-520.","DOI":"10.1006\/mcne.1995.0003"},{"key":"2021042517480795600_REF5","doi-asserted-by":"crossref","unstructured":"Bernier, G., Mathieu, M., de Repentigny, Y., Vidal, S. M. and Kothary, R. (1996). Cloning and characterization of mouse ACF7, a novel member of the dystonin subfamily of actin binding proteins. Genomics38, 19-29.","DOI":"10.1006\/geno.1996.0587"},{"key":"2021042517480795600_REF6","doi-asserted-by":"crossref","unstructured":"Brown, A., Bernier, G., Mathieu, M., Rossant, J. and Kothary, R. (1995). The mouse dystonia musculorum gene is a neural isoform of bullous pemphigoid antigen 1. Nat. Genet.10, 301-306.","DOI":"10.1038\/ng0795-301"},{"key":"2021042517480795600_REF7","doi-asserted-by":"crossref","unstructured":"Collavin, L., Buzzai, M., Saccone, S., Bernard, L., Federico, C., DellaValle, G., Brancolini, C. and Schneider, C. (1998). cDNA characterization and chromosome mapping of the human GAS2 gene. Genomics48, 265-269.","DOI":"10.1006\/geno.1997.5172"},{"key":"2021042517480795600_REF8","doi-asserted-by":"crossref","unstructured":"Dalpe\u0301, G., Leclerc, N., Vallee, A., Messer, A., Mathieu, M., de Repentigny, Y. and Kothary, R. (1998). Dystonin is essential for maintaining neuronal cytoskeleton organization. Mol. Cell. Neurosci.10, 243-257.","DOI":"10.1006\/mcne.1997.0660"},{"key":"2021042517480795600_REF9","doi-asserted-by":"crossref","unstructured":"Dalpe\u0301, G., Mathieu, M., Comtois, A., Zhu, E., Wasiak, S., de Repentigny, Y., Leclerc, N. and Kothary, R. (1999). Dystonin-deficient mice exhibit an intrinsic muscle weakness and an instability of skeletal muscle cytoarchitecture. Dev. Biol.210, 367-380.","DOI":"10.1006\/dbio.1999.9263"},{"key":"2021042517480795600_REF10","doi-asserted-by":"crossref","unstructured":"Dubreuil, R. R., Byers, T. J., Stewart, C. T. and Kiehart, D. P. (1990). A beta-spectrin isoform from Drosophila (beta H) is similar in size to vertebrate dystrophin. J. Cell Biol.111, 1849-1858.","DOI":"10.1083\/jcb.111.5.1849"},{"key":"2021042517480795600_REF11","doi-asserted-by":"crossref","unstructured":"Duchen, L. W. and Strich, S. J. (1964). Clinical and pathological studies of an hereditary neuropathy in mice. Brain87, 367-378.","DOI":"10.1093\/brain\/87.2.367"},{"key":"2021042517480795600_REF12","unstructured":"Duchen, L. W., Falconer, D. S. and Strich, S. J. (1963). Dystonia Musculorum. A hereditary neuropathy of mice affecting mainly sensory pathways. J. Physiol.165, 7-9."},{"key":"2021042517480795600_REF13","doi-asserted-by":"crossref","unstructured":"Favre, B., Fontao, L., Koster, J., Shafaatian, R., Jaunin, F., Saurat, J. H., Sonnenberg, A. and Borradori, L. (2001). The hemidesmosomal proteins bullous pemphigoid antigen 1 and the integrin beta 4 subunit bind to ERBIN. J. Biol. Chem.276, 32427-32436.","DOI":"10.1074\/jbc.M011005200"},{"key":"2021042517480795600_REF14","doi-asserted-by":"crossref","unstructured":"Fontao, L., Geerts, D., Kuikman, I., Koster, J., Kramer, D. and Sonnenberg, A. (2001). The interaction of plectin with actin: evidence for cross-linking of actin filaments by dimerization of the actin-binding domain of plectin. J. Cell Sci.114, 2065-2076.","DOI":"10.1242\/jcs.114.11.2065"},{"key":"2021042517480795600_REF15","doi-asserted-by":"crossref","unstructured":"Fuchs, E. and Yang, Y. (1999). Crossroads on cytoskeletal highways. 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Cell81, 233-243.","DOI":"10.1016\/0092-8674(95)90333-X"},{"key":"2021042517480795600_REF19","doi-asserted-by":"crossref","unstructured":"Hopkinson, S. B. and Jones, J. C. (2000). The N terminus of the transmembrane protein BP180 interacts with the N-terminal domain of BP230, thereby mediating keratin cytoskeleton anchorage to the cell surface at the site of the hemidesmosome. Mol. Biol. Cell11, 277-286.","DOI":"10.1091\/mbc.11.1.277"},{"key":"2021042517480795600_REF20","doi-asserted-by":"crossref","unstructured":"Ishiko, A., Shimizu, H., Kikuchi, A., Ebihara, T., Hashimoto, T. and Nishikawa, T. (1993). Human autoantibodies against the 230-kD bullous pemphigoid antigen (BPAG1) bind only to the intracellular domain of the hemidesmosome, whereas those against the 180-kD bullous pemphigoid antigen (BPAG2) bind along the plasma membrane of the hemidesmosome in normal human and swine skin. J. Clin. Invest.91, 1608-1615.","DOI":"10.1172\/JCI116368"},{"key":"2021042517480795600_REF21","doi-asserted-by":"crossref","unstructured":"Jones, J. C., Asmuth, J., Baker, S. E., Langhofer, M., Roth, S. I. and Hopkinson, S. B. (1994). Hemidesmosomes: extracellular matrix\/intermediate filament connectors. Exp. Cell Res.213, 1-11.","DOI":"10.1006\/excr.1994.1166"},{"key":"2021042517480795600_REF22","doi-asserted-by":"crossref","unstructured":"Karakesisoglou, I., Yang, Y. and Fuchs, E. (2000). An epidermal plakin that integrates actin and microtubule networks at cellular junctions. J. Cell Biol.149, 195-208.","DOI":"10.1083\/jcb.149.1.195"},{"key":"2021042517480795600_REF23","doi-asserted-by":"crossref","unstructured":"Klymkowsky, M. W. (1999). Weaving a tangled web: the interconnected cytoskeleton. Nat. Cell Biol.1, E121-123.","DOI":"10.1038\/12950"},{"key":"2021042517480795600_REF24","doi-asserted-by":"crossref","unstructured":"Koenig, M., Hoffman, E. P., Bertelson, C. J., Monaco, A. P., Feener, C. and Kunkel, L. M. (1987). Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell50, 509-517.","DOI":"10.1016\/0092-8674(87)90504-6"},{"key":"2021042517480795600_REF25","doi-asserted-by":"crossref","unstructured":"Koster, J., Geerts, D., Favre, B., Borradori, L. and Sonnenberg, A. (2003). Analysis of the interactions between BP180, BP230, plectin and the integrin alpha6beta4 important for hemidesmosome assembly. J. Cell Sci.116, 387-399.","DOI":"10.1242\/jcs.00241"},{"key":"2021042517480795600_REF26","doi-asserted-by":"crossref","unstructured":"Laemmli, U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature227, 680-685.","DOI":"10.1038\/227680a0"},{"key":"2021042517480795600_REF27","doi-asserted-by":"crossref","unstructured":"Leung, C. L., Sun, D. and Liem, R. K. (1999a). The intermediate filament protein peripherin is the specific interaction partner of mouse BPAG1-n (dystonin) in neurons. J. Cell Biol.144, 435-446.","DOI":"10.1083\/jcb.144.3.435"},{"key":"2021042517480795600_REF28","doi-asserted-by":"crossref","unstructured":"Leung, C. L., Sun, D., Zheng, M., Knowles, D. R. and Liem, R. K. (1999b). Microtubule actin cross-linking factor (MACF): a hybrid of dystonin and dystrophin that can interact with the actin and microtubule cytoskeletons. J. Cell Biol.147, 1275-1286.","DOI":"10.1083\/jcb.147.6.1275"},{"key":"2021042517480795600_REF29","doi-asserted-by":"crossref","unstructured":"Leung, C. L., Zheng, M., Prater, S. M. and Liem, R. K. (2001). The BPAG1 locus: alternative splicing produces multiple isoforms with distinct cytoskeletal linker domains, including predominant isoforms in neurons and muscles. J. Cell Biol.154, 691-698.","DOI":"10.1083\/jcb.200012098"},{"key":"2021042517480795600_REF30","doi-asserted-by":"crossref","unstructured":"Mueller, S., Klaus-Kovtun, V. and Stanley, J. R. (1989). A 230-kD basic protein is the major bullous pemphigoid antigen. J. Invest. Dermatol.92, 33-38.","DOI":"10.1111\/1523-1747.ep13070476"},{"key":"2021042517480795600_REF31","doi-asserted-by":"crossref","unstructured":"Mutasim, D. F., Takahashi, Y., Labib, R. S., Anhalt, G. J., Patel, H. P. and Diaz, L. A. (1985). A pool of bullous pemphigoid antigen(s) is intracellular and associated with the basal cell cytoskeleton-hemidesmosome complex. J. Invest. Dermatol.84, 47-53.","DOI":"10.1111\/1523-1747.ep12274684"},{"key":"2021042517480795600_REF32","doi-asserted-by":"crossref","unstructured":"Nikolic, B., MacNulty, E., Mir, B. and Wiche, G. (1996). Basic amino acid residue cluster within nuclear targeting sequence motif is essential for cytoplasmic plectin-vimentin network junctions. J. Cell Biol.134, 1455-1467.","DOI":"10.1083\/jcb.134.6.1455"},{"key":"2021042517480795600_REF33","doi-asserted-by":"crossref","unstructured":"Noegel, A., Witke, W. and Schleicher, M. (1987). Calcium-sensitive nonmuscle alpha-actinin contains EF-hand structures and highly conserved regions. FEBS Lett.221, 391-396.","DOI":"10.1016\/0014-5793(87)80962-6"},{"key":"2021042517480795600_","doi-asserted-by":"crossref","unstructured":"Schulter, C., Duchrow, M., Wohlenberg, C., Becker, M. H. G., Key, G., Flad, H.-D. and Gerdes, J. (1993). The cell proliferation-associated antigen of antibody Ki-67: A very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins. J. Cell Biol.123, 513-522.","DOI":"10.1083\/jcb.123.3.513"},{"key":"2021042517480795600_REF35","doi-asserted-by":"crossref","unstructured":"Stanley, J. R., Tanaka, T., Mueller, S., Klaus-Kovtun, V. and Roop, D. (1988). Isolation of complementary DNA for bullous pemphigoid antigen by use of patients' autoantibodies. J. Clin. Invest.82, 1864-1870.","DOI":"10.1172\/JCI113803"},{"key":"2021042517480795600_REF36","doi-asserted-by":"crossref","unstructured":"Sun, D., Leung, C. L. and Liem, R. K. (2001). Characterization of the microtubule binding domain of microtubule actin crosslinking factor (MACF): identification of a novel group of microtubule associated proteins. J. Cell Sci.114, 161-172.","DOI":"10.1242\/jcs.114.1.161"},{"key":"2021042517480795600_REF37","doi-asserted-by":"crossref","unstructured":"van den Heuvel, A. P., de Vries-Smits, A. M., van Weeren, P. C., Dijkers, P. F., de Bruyn, K. M., Riedl, J. A. and Burgering, B. M. (2002). Binding of protein kinase B to the plakin family member periplakin. J. Cell Sci.115, 3957-3966.","DOI":"10.1242\/jcs.00069"},{"key":"2021042517480795600_REF38","doi-asserted-by":"crossref","unstructured":"van der Flier, A., Kuikman, I., Kramer, D., Geerts, D., Kreft, M., Takafuta, T., Shapiro, S. S. and Sonnenberg, A. (2002). Different splice variants of filamin-B affect myogenesis, subcellular distribution, and determine binding to integrin [beta] subunits. J. Cell Biol.156, 361-376.","DOI":"10.1083\/jcb.200103037"},{"key":"2021042517480795600_REF39","doi-asserted-by":"crossref","unstructured":"Wiche, G. (1998). Role of plectin in cytoskeleton organization and dynamics. J. Cell Sci.111, 2477-2486.","DOI":"10.1242\/jcs.111.17.2477"},{"key":"2021042517480795600_REF40","doi-asserted-by":"crossref","unstructured":"Witke, W., Schleicher, M., Lottspeich, F. and Noegel, A. (1986). Studies on the transcription, translation, and structure of alpha-actinin in Dictyostelium discoideum. J. Cell Biol.103, 969-975.","DOI":"10.1083\/jcb.103.3.969"},{"key":"2021042517480795600_REF41","doi-asserted-by":"crossref","unstructured":"Yang, Y., Dowling, J., Yu, Q. C., Kouklis, P., Cleveland, D. W. and Fuchs, E. (1996). An essential cytoskeletal linker protein connecting actin microfilaments to intermediate filaments. Cell86, 655-665.","DOI":"10.1016\/S0092-8674(00)80138-5"},{"key":"2021042517480795600_REF42","doi-asserted-by":"crossref","unstructured":"Yang, Y., Bauer, C., Strasser, G., Wollman, R., Julien, J. P. and Fuchs, E. (1999). Integrators of the cytoskeleton that stabilize microtubules. Cell98, 229-238.","DOI":"10.1016\/S0092-8674(00)81017-X"},{"key":"2021042517480795600_REF43","doi-asserted-by":"crossref","unstructured":"Zucman-Rossi, J., Legoix, P. and Thomas, G. (1996). Identification of new members of the Gas2 and Ras families in the 22q12 chromosome region. Genomics38, 247-254.","DOI":"10.1006\/geno.1996.0625"}],"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/116\/22\/4543\/1493495\/4543.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/116\/22\/4543\/1493495\/4543.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,12]],"date-time":"2021-06-12T05:06:51Z","timestamp":1623474411000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/116\/22\/4543\/27356\/Bpag1-localization-to-actin-filaments-and-to-the"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,11,15]]},"references-count":43,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2003,11,15]]}},"URL":"https:\/\/doi.org\/10.1242\/jcs.00764","relation":{},"ISSN":["1477-9137","0021-9533"],"issn-type":[{"value":"1477-9137","type":"electronic"},{"value":"0021-9533","type":"print"}],"subject":[],"published":{"date-parts":[[2003,11,15]]}}}