{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T13:09:11Z","timestamp":1774616951674,"version":"3.50.1"},"reference-count":53,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":1598,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["NO 113\/26 and SFB670, TP1"],"award-info":[{"award-number":["NO 113\/26 and SFB670, TP1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Mutations in tripeptidyl peptidase 1 (TPP1) have been associated with late infantile neuronal ceroid lipofuscinosis (NCL2), a neurodegenerative disorder. TPP1 is a lysosomal serine protease, which removes tripeptides from the amino terminus of proteins and is composed of an N-terminal prodomain and a catalytic domain. It is conserved in mammals, amphibians, fish and the amoeba Dictyostelium discoideum. D. discoideum harbors at least six genes encoding tripeptidyl peptidase 1, tpp1A to tpp1F. We identified TPP1F as binding partner of Dictyostelium GPHR (Golgi pH regulator), which is an evolutionary highly conserved intracellular transmembrane protein. For the interaction, a region encompassing the DUF3735 (GPHR_N) domain of GPHR was responsible. In TPP1F the binding site was located in the prodomain. The Tpp1F gene is transcribed throughout development and translated into a polypeptide of approximately 65 kDa. TPP1 activity was demonstrated for TPP1F-GFP immunoprecipitated from D. discoideum cells. Its activity could be inhibited by addition of the recombinant DUF3735 domain of GPHR. Knockout tpp1F mutants did not display a particular phenotype and TPP1 activity was not abrogated, which is presumably due to expression of Tpp1B showing the highest expression levels of all Tpp1 genes during growth. The GPHR interaction was not restricted to TPP1F but occurred also with TPP1B. Based on previous reports showing that the majority of the TPP1 mutations in NCL2 resulted in reduction or loss of enzyme activity, our findings may help to create new reagents with which one can affect the activity of the protein and ameliorate the disease.<\/jats:p>","DOI":"10.1242\/dmm.029280","type":"journal-article","created":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T00:30:26Z","timestamp":1495758626000},"source":"Crossref","is-referenced-by-count":11,"title":["A Tripeptidyl peptidase 1 is a binding partner of GPHR (Golgi pH regulator) in <i>Dictyostelium<\/i>"],"prefix":"10.1242","author":[{"given":"Maria","family":"Stumpf","sequence":"first","affiliation":[{"name":"Institute of Biochemistry I, Medical Faculty, University Hospital Cologne, University of Cologne, Joseph-Stelzmann-Str. 52, 50931 K\u00f6ln, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolf","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry I, Medical Faculty, University Hospital Cologne, University of Cologne, Joseph-Stelzmann-Str. 52, 50931 K\u00f6ln, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Berthold","family":"Ga\u00dfen","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry I, Medical Faculty, University Hospital Cologne, University of Cologne, Joseph-Stelzmann-Str. 52, 50931 K\u00f6ln, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina","family":"Wehrstedt","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry I, Medical Faculty, University Hospital Cologne, University of Cologne, Joseph-Stelzmann-Str. 52, 50931 K\u00f6ln, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Fey","sequence":"additional","affiliation":[{"name":"dicty Base, Northwestern University, Biomedical Informatics Center and Center for Genetic Medicine, Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malte A.","family":"Karow","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry I, Medical Faculty, University Hospital Cologne, University of Cologne, Joseph-Stelzmann-Str. 52, 50931 K\u00f6ln, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ludwig","family":"Eichinger","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry I, Medical Faculty, University Hospital Cologne, University of Cologne, Joseph-Stelzmann-Str. 52, 50931 K\u00f6ln, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gernot","family":"Gl\u00f6ckner","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry I, Medical Faculty, University Hospital Cologne, University of Cologne, Joseph-Stelzmann-Str. 52, 50931 K\u00f6ln, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8260-6732","authenticated-orcid":false,"given":"Angelika A.","family":"Noegel","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry I, Medical Faculty, University Hospital Cologne, University of Cologne, Joseph-Stelzmann-Str. 52, 50931 K\u00f6ln, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2017,1,1]]},"reference":[{"key":"2021042500164457400_DMM029280C1","doi-asserted-by":"publisher","first-page":"2556","DOI":"10.1002\/pmic.200900516","article-title":"The secreted proteome profile of developing Dictyostelium discoideum cells","volume":"10","author":"Bakthavatsalam","year":"2010","journal-title":"Proteomics"},{"key":"2021042500164457400_DMM029280C2","doi-asserted-by":"publisher","first-page":"2242","DOI":"10.1016\/j.bbadis.2015.04.027","article-title":"Cell biology of the NCL proteins: what they do and don't do","volume":"1852","author":"C\u00e1rcel-Trullols","year":"2015","journal-title":"Biochim. 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