title: Trans-Golgi network morphology and sorting is regulated by prolyl-oligopeptidase-like protein PREPL and the AP-1 complex subunit μ1A.
abstract: The AP-1 complex recycles between membranes and the cytoplasm and dissociates from membranes during clathrin-coated-vesicle uncoating, but also independently of vesicular transport. The μ1A N-terminal 70 amino acids are involved in regulating AP-1 recycling. In a yeast two-hybrid library screen we identified the cytoplasmic prolyl-oligopeptidase-like protein PREPL as an interaction partner of this domain. PREPL overexpression leads to reduced AP-1 membrane binding, whereas reduced PREPL expression increases membrane binding and impairs AP-1 recycling. Altered AP-1 membrane binding in PREPL-deficient cells mirrors the membrane binding of the mutant AP-1* complex, which is not able to bind PREPL. Colocalisation of PREPL with residual membrane-bound AP-1 can be demonstrated. Patient cell lines deficient in PREPL have an expanded trans-Golgi network, which could be rescued by PREPL expression. These data demonstrate PREPL as an AP-1 effector that takes part in the regulation of AP-1 membrane binding. PREPL is highly expressed in brain and at lower levels in muscle and kidney. Its deficiency causes hypotonia and growth hormone hyposecretion, supporting essential PREPL functions in AP-1-dependent secretory pathways.
authors: Georg-August-University Göttingen, Center for Biochemistry and Moleculare Cell Biology, Biochemie II, Humboldtallee 23, 37073 Göttingen, Germany.
authors: Karthikeyan
authors: K
authors: Radhakrishnan
authors: Jennifer
authors: J
authors: Baltes
authors: John W M
authors: JW
authors: Creemers
authors: Peter
authors: P
authors: Schu
mesh_terms: D034001:Adaptor Protein Complex Subunits / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002966:Clathrin / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D007668:Kidney / Q000378:metabolism; D051379:Mice; D009132:Muscles / Q000378:metabolism; D000085822:Prolyl Oligopeptidases; D011485:Protein Binding; D012697:Serine Endopeptidases / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D021601:trans-Golgi Network / Q000378:metabolism*
chemical_list: D034001:Adaptor Protein Complex Subunits; D002966:Clathrin; D018808:Transcription Factor AP-1; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases