{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:03:30Z","timestamp":1790705010415,"version":"4.1.0"},"reference-count":77,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T00:00:00Z","timestamp":1606694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001655","name":"Deutscher Akademischer Austauschdienst","doi-asserted-by":"publisher","award":["91534725 to A.A.H."],"award-info":[{"award-number":["91534725 to A.A.H."]}],"id":[{"id":"10.13039\/501100001655","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["BR 1308\/6-1, 6-2 to K.B."],"award-info":[{"award-number":["BR 1308\/6-1, 6-2 to K.B."]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014757","name":"Jacobs University","doi-asserted-by":"publisher","award":["6113\/90140 to K.B."],"award-info":[{"award-number":["6113\/90140 to K.B."]}],"id":[{"id":"10.13039\/501100014757","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The significance of cysteine cathepsins for the liberation of thyroid hormones from the precursor thyroglobulin was previously shown by in vivo and in vitro studies. Cathepsin L is most important for thyroglobulin processing in mice. The present study aims at specifying the possible contribution of its closest relative, cysteine cathepsin L2\/V, to thyroid function. Immunofluorescence analysis on normal human thyroid tissue revealed its predominant localization at the apical plasma membrane of thyrocytes and within the follicle lumen, indicating the secretion of cathepsin V and extracellular tasks rather than its acting within endo-lysosomes. To explore the trafficking pathways of cathepsin V in more detail, a chimeric protein consisting of human cathepsin V tagged with green fluorescent protein (GFP) was stably expressed in the Nthy-ori 3-1 thyroid epithelial cell line. Colocalization studies with compartment-specific markers and analyses of post-translational modifications revealed that the chimeric protein was sorted into the lumen of the endoplasmic reticulum and subsequently transported to the Golgi apparatus, while being N-glycosylated. Immunoblotting showed that the chimeric protein reached endo-lysosomes and it became secreted from the transduced cells. Astonishingly, thyroid stimulating hormone (TSH)-induced secretion of GFP-tagged cathepsin V occurred as the proform, suggesting that TSH upregulates its transport to the plasma membrane before it reaches endo-lysosomes for maturation. The proform of cathepsin V was found to be reactive with the activity-based probe DCG-04, suggesting that it possesses catalytic activity. We propose that TSH-stimulated secretion of procathepsin V is the default pathway in the thyroid to enable its contribution to thyroglobulin processing by extracellular means.<\/jats:p>","DOI":"10.3390\/ijms21239140","type":"journal-article","created":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T20:10:22Z","timestamp":1606767022000},"page":"9140","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Procathepsin V Is Secreted in a TSH Regulated Manner from Human Thyroid Epithelial Cells and Is Accessible to an Activity-Based Probe"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4034-5102","authenticated-orcid":false,"given":"Alaa","family":"Al-Hashimi","sequence":"first","affiliation":[{"name":"Department of Life Sciences and Chemistry, Jacobs University Bremen, D-28759 Bremen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6772-6787","authenticated-orcid":false,"given":"Vaishnavi","family":"Venugopalan","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Chemistry, Jacobs University Bremen, D-28759 Bremen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7854-0977","authenticated-orcid":false,"given":"Maren","family":"Rehders","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Chemistry, Jacobs University Bremen, D-28759 Bremen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naphannop","family":"Sereesongsaeng","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen\u2019s University Belfast, Belfast BT9 7BL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6335-8961","authenticated-orcid":false,"given":"Zeynep","family":"Hein","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Chemistry, Jacobs University Bremen, D-28759 Bremen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5527-6149","authenticated-orcid":false,"given":"Sebastian","family":"Springer","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Chemistry, Jacobs University Bremen, D-28759 Bremen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4014-4303","authenticated-orcid":false,"given":"Ekkehard","family":"Weber","sequence":"additional","affiliation":[{"name":"Institute of Physiological Chemistry, Martin Luther University Halle-Wittenberg, D-06114 Halle-Saale, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"F\u00fchrer","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Endokrinologie, Diabetologie und Stoffwechsel, Universit\u00e4tsklinikum Essen (A\u00f6R), Universit\u00e4t Duisburg-Essen, D-45177 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3753-4412","authenticated-orcid":false,"given":"Matthew S.","family":"Bogyo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5324, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7582-3808","authenticated-orcid":false,"given":"Christopher J.","family":"Scott","sequence":"additional","affiliation":[{"name":"Patrick G. Johnston Centre for Cancer Research, School of Medicine, Dentistry and Biomedical Sciences, Queen\u2019s University Belfast, Belfast BT9 7BL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3731-7939","authenticated-orcid":false,"given":"Roberta E.","family":"Burden","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen\u2019s University Belfast, Belfast BT9 7BL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4476-0357","authenticated-orcid":false,"given":"Klaudia","family":"Brix","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Chemistry, Jacobs University Bremen, D-28759 Bremen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1021\/bi982175f","article-title":"Human cathepsin V functional expression, tissue distribution, electrostatic surface potential, enzymatic characterization, and chromosomal localization","volume":"38","author":"Li","year":"1999","journal-title":"Biochemistry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1515\/BC.2004.040","article-title":"Comprehensive search for cysteine cathepsins in the human genome","volume":"385","author":"Rossi","year":"2004","journal-title":"Biol. 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