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Storage of TG within the follicle lumen is achieved by compactation and by the formation of covalent cross\u2010links between TG molecules. In bovine thyroids, ~75% of the cross\u2010links are other than disulfide bonds (J. Cell Biol. 180, 1071\u20131081). We have now shown that polymeric TG contains a large number of N\n                    <jats:sup>\u03b5<\/jats:sup>\n                    (\u03b3\u2010glutamyl)lysine cross\u2010links and that only traces of these can be found in the soluble form of TG. Because such isopeptide bridges are generated usually by the action of a transglutaminase, it is reasonable to propose that the covalent polymerization of TG in the globules is under the control of this enzyme. Soluble TG was shown to be a substrate for transglutaminase\n                    <jats:italic>in vitro;<\/jats:italic>\n                    moreover, the presence of transglutaminase was demonstrated by immunofluo\u2010rescence and by immunoblotting in freshly isolated bovine thyroid globules. With immunoelectron microscopy, transglutaminase was detected in the cytoplasm of thyrocytes, but not in compartments of the secretory pathway. Only one messenger RNA for transglutaminase was found by Northern blotting. Sequencing of the cloned gene failed to reveal a secretory signal, which supports the notion that the thyroid transglutaminase is the cytosolic type. Apparently, the enzyme reaches the lumen of the follicle by an as yet unknown pathway to catalyze the covalent cross\u2010linking of thyroid globules in this extracellular compartment.\u2014Saber\u2010Lichtenberg, Y., Brix, K., Schmitz, A., Heuser, J. E., Wilson, J. H., Lorand, L., and Herzog, V. Covalent cross\u2010linking of secreted bovine thyroglobulin by transglutaminase\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    14, 1005\u20131014 (2000)\n                  <\/jats:p>","DOI":"10.1096\/fasebj.14.7.1005","type":"journal-article","created":{"date-parts":[[2018,1,18]],"date-time":"2018-01-18T08:36:10Z","timestamp":1516264570000},"page":"1005-1014","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Covalent cross\u2010linking of secreted bovine thyroglobulin by transglutaminase"],"prefix":"10.1096","volume":"14","author":[{"given":"Yasmin","family":"Saber\u2010Lichtenberg","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Zellbiologie Universit\u00e4t Bonn  Ulrich\u2010Haberland\u2010Str. 61a D\u201053121 Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaudia","family":"Brix","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Zellbiologie Universit\u00e4t Bonn  Ulrich\u2010Haberland\u2010Str. 61a D\u201053121 Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Zellbiologie Universit\u00e4t Bonn  Ulrich\u2010Haberland\u2010Str. 61a D\u201053121 Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Heuser","sequence":"additional","affiliation":[{"name":"Washington University, School of Medicine Department of Cell Biology  St. Louis Missouri 63110 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James H.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Northwestern University, Medical School Department of Cell and Molecular Biology  Chicago Illinois 60611 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laszlo","family":"Lorand","sequence":"additional","affiliation":[{"name":"Northwestern University, Medical School Department of Cell and Molecular Biology  Chicago Illinois 60611 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Herzog","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Zellbiologie Universit\u00e4t Bonn  Ulrich\u2010Haberland\u2010Str. 61a D\u201053121 Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2000,5]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"1325","volume-title":"In Metabolic Control and Disease","author":"Robbins J.","year":"1980"},{"key":"e_1_2_6_3_1","first-page":"59","volume-title":"Thyroid Diseases: Basic Science, Pathology, Clinical and Laboratory Diagnoses","author":"Kohn L. 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