Investigation of cellular mechanisms of Ser9Leu proopiomelanocortin (POMC) mutation in neuronal cells

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2019

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Vural, Merve

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Pro-opiomelanocortin (POMC) is a precursor protein and synthesized in many different tissues of the body. It is proteolytically cleaved into different biologically active peptides which have different physiological functions based on the tissues they are found. Some of these peptides act in the brain to reduce food intake. The main regulator of the food intake and energy homeostasis is the arcuate nucleus (ARC) within the hypothalamus, and hypothalamic neurons expressing POMC have important roles in the regulation of body weight and energy homeostasis. These neurons are stimulated by the signals from extracellular matrix (ECM) to release the contents of mature POMC vesicles. The active peptides of POMC are released into the ECM and lead to anorexigenic response which suppress the food intake. Due to the important role of POMC in the regulation of body weight, many studies have focused on mutations in POMC of obese people. One of these mutations is Ser9Leu POMC found among children having early-onset obesity. It is located in the signal peptide of POMC which is removed after the co-translation of the protein in the normal state of the cell. In this study, the cellular mechanisms of the Ser9Leu POMC mutation were investigated. It was hypothesized that Ser9Leu POMC inhibits the translocation of POMC into the endoplasmic reticulum (ER) and leads to the accumulation of mutant proteins which may be secreted in the constitutive secretory pathway. Therefore, mouse neuroblastoma cells (N2a) were transfected with wild-type and Ser9Leu POMC DNAs, and secreted proteins from N2a cells were analyzed with the Western blot method using anti-ACTH (adrenocorticotropic hormone). Results revealed that the Ser9Leu POMC mutation did not cause a different effect on the cellular mechanism for its secretion from the neuronal cells.

Subject Keywords

Proopiomelanocortin., Neural stem cells., Neurons., Obesity.

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http://etd.lib.metu.edu.tr/upload/12623020/index.pdf
https://hdl.handle.net/11511/27938

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Graduate School of Natural and Applied Sciences, Thesis

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Citation Formats

M. Vural, “Investigation of cellular mechanisms of Ser9Leu proopiomelanocortin (POMC) mutation in neuronal cells,” M.S. - Master of Science, Middle East Technical University, 2019.