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: Karthikeyan Radhakrishnan, Jennifer Baltes, John W M Creemers, Peter Schu
• Journal: Journal of cell science (J Cell Sci) Vol. 126 Issue Pt 5 Pg. 1155-63 (Mar 01 2013) ISSN: 1477-9137 [Electronic] England
• PMID: 23321636 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Protein Complex Subunits
• Clathrin
• Transcription Factor AP-1
• Serine Endopeptidases
• PREPL protein, human
• Prolyl Oligopeptidases

Topics

• Adaptor Protein Complex Subunits (metabolism)
• Animals
• Brain (metabolism)
• Cell Line
• Clathrin (metabolism)
• Humans
• Immunoprecipitation
• Kidney (metabolism)
• Mice
• Muscles (metabolism)
• Prolyl Oligopeptidases
• Protein Binding
• Serine Endopeptidases (metabolism)
• Transcription Factor AP-1 (metabolism)
• trans-Golgi Network (metabolism)