Universität zu Köln

Stumpf, Maria, Mueller, Rolf, Gassen, Berthold, Wehrstedt, Regina, Fey, Petra ORCID: 0000-0002-4532-2703, Karow, Malte A., Eichinger, Ludwig ORCID: 0000-0003-1594-6117, Gloeckner, Gernot and Noegel, Angelika A. (2017). A tripeptidyl peptidase 1 is a binding partner of the Golgi pH regulator (GPHR) in Dictyostelium. Dis. Model. Mech., 10 (7). S. 897 - 908. CAMBRIDGE: COMPANY BIOLOGISTS LTD. ISSN 1754-8411

Full text not available from this repository.

Abstract

Mutations in tripeptidyl peptidase 1 (TPP1) have been associated with late infantile neuronal ceroid lipofuscinosis (NCL), a neurodegenerative disorder. TPP1 is a lysosomal serine protease, which removes tripeptides from the N-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 TPP1, tpp1A to tpp1F. We identified TPP1F as binding partner of Dictyostelium GPHR (Golgi pH regulator), which is an evolutionarily highly conserved intracellular transmembrane protein. A region encompassing the DUF3735 (GPHR_N) domain of GPHR was responsible for the interaction. In TPP1F, the binding site is located in the prodomain of the protein. The tpp1F gene is transcribed throughout development and translated into a polypeptide of similar to 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 any particular phenotype, and TPP1 activity was not abrogated, presumably because tpp1B compensates as it has the highest expression level of all the TPP1 genes during growth. The GPHR interaction was not restricted to TPP1F but occurred also with TPP1B. As previous reports show that the majority of the TPP1 mutations in NCL resulted in reduction or loss of enzyme activity, we suggest that Dicyostelium could be used as a model system in which to test new reagents that could affect the activity of the protein and ameliorate the disease.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Stumpf, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Rolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Gassen, Berthold UNSPECIFIED UNSPECIFIED UNSPECIFIED Wehrstedt, Regina UNSPECIFIED UNSPECIFIED UNSPECIFIED Fey, Petra UNSPECIFIED orcid.org/0000-0002-4532-2703 UNSPECIFIED Karow, Malte A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Eichinger, Ludwig UNSPECIFIED orcid.org/0000-0003-1594-6117 UNSPECIFIED Gloeckner, Gernot UNSPECIFIED UNSPECIFIED UNSPECIFIED Noegel, Angelika A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-225979
DOI:	10.1242/dmm.029280
Journal or Publication Title:	Dis. Model. Mech.
Volume:	10
Number:	7
Page Range:	S. 897 - 908
Date:	2017
Publisher:	COMPANY BIOLOGISTS LTD
Place of Publication:	CAMBRIDGE
ISSN:	1754-8411
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NEURONAL CEROID-LIPOFUSCINOSIS; SOCIAL AMEBA DICTYOSTELIUM; CYCLASE-ASSOCIATED PROTEIN; ENDOPLASMIC-RETICULUM; CARBOXYL PROTEINASE; DISCOIDEUM; SEQUENCE; GENE; TRANSCRIPTOMES; PURIFICATION Multiple languages Cell Biology; Pathology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22597