The role of PREPL in regulated secretion and neuromuscular transmission.

The Hypotonia-Cystinuria syndrome is caused by deletions of the Prolyl Endopeptidase-like (PREPL)</> and SLC3A1</> genes on chromosome 2p21. This recessive metabolic syndrome is characterized by cystinuria, neonatalhypotonia and growth hormone deficiency. Since it is well established that inactivating mutations or deletions in the SLC3A1</> gene cause isolated cystinuria, all other symptoms can be attributed to the deletion ofPREPL</>. How PREPL</> deficiency causes these clinical manifestations is currently unknown. Based on its homology with PREP (Prolyl EndoPeptidase), PREPL</> was predicted to encode an oligopeptidase. Although activity of the catalytic machinery has been demonstrated, no peptide substrates have been identified so far. Preliminary results suggest that PREPL is involved in neuromuscular transmission and regulated secretion, whichcorresponds to the observed symptoms in HCS patients. Therefore, the aim of this research is to characterize the function of PREPL in regulatedsecretion in neuroencrine cell lines, as well as at the neuromuscular junction, in hippocampal neurons and somatotrophs of a PREPL KO mouse model. </>

Keywords:Hypotonia-Cystinuria Syndrome, Neuromuscular transmission, PREPL, HCS, Prolyl Endopeptidase-like, Regulated secretion

Disciplines:Other biological sciences, Genetics, Systems biology, Molecular and cell biology, Endocrinology and metabolic diseases

Project type:PhD project