You are cordially invited to the first Neuroscience Department & National Magnetic Research Center (UMRAM) seminar of the academic year.
These seminars provide an opportunity for everyone interested in the interdisciplinary fields of Neuroscience and MR Imaging to come together, learn about the most recent advances, and have a chance to meet and interact with fellow members of our community. This first seminar will be delivered by Fulya Türker from the Molecular Biology and Genetics department at Bilkent University.
Date: November 7, 2024 (Thursday)
Time and Venue: 16:30, NSC & UMRAM Conference Room (SC-06) Snacks and beverages will be available
Title: Identification of neuronal membrane proteasome-derived peptides that modulate neuronal signaling
Abstract: Protein homeostasis is essential for maintaining cellular health. Proteins are synthesized and eventually degraded to balance protein levels in all cells. The main non-lysosomal protein degradation machinery in eukaryotic cells is the proteasome, a large macromolecule equipped with proteases responsible for the breakdown of proteins and production of peptide fragments. Strikingly, exclusively in neurons, the proteasome can localize to the plasma membrane, where it degrades newly synthesized intracellular proteins into extracellular peptides. This unique co-translational degradation mechanism highlights a distinct role for neuronal membrane proteasomes (NMPs). Selective inhibition of the NMP complex halts peptide release and rapidly attenuates neuronal transmission. Based on these findings, we hypothesized that NMP peptides mediate a novel form of communication through specific peptide-receptor interactions to promote intracellular signaling cascades relevant to neuronal development and function. Our work indicates that purified NMP peptides, once applied to naïve neurons, rapidly induce N-methyl-D-aspartate receptor (NMDAR)-dependent calcium influx, leading to sustained phosphorylation of the activity-dependent transcription factor cAMP response element-binding protein (CREB). We also determined that the gene expression program and the proteome pool drastically change upon NMP peptide treatment with increased expression of activity-regulated genes (e.g., Fos, Npas4, Egr4) known to have critical neuroregulatory roles. This pathway is parallel to classic neuronal activity-dependent programs and points to NMP and its resulting endogenous peptides as potential key modulators of neuronal function in health and disease. Further elucidation of the regulatory mechanisms governing the NMP complex, and identification of its bioactive peptide products are critical steps toward fully understanding this novel signaling process in the mammalian nervous system.
Bio: Dr. Türker graduated with a B.Sc. in Molecular Biology, Genetics, and Bioengineering, and a minor in Chemistry, from Sabancı University in Istanbul, Turkey in 2017. During her undergraduate studies, she spent a semester as an exchange student at Boston University and interning at Harvard Medical School. She then pursued her Ph.D. in the Department of Biological Chemistry at Johns Hopkins University School of Medicine, under the mentorship of Dr. Seth Margolis. Her doctoral research focused on identifying neuronal membrane proteasome-derived peptides with signaling capabilities in the nervous system. Additionally, she explored dynamics of proteasome’s enzymatic functions in neurodegenerative diseases through the use of activity-based probes. After earning her Ph.D., Dr. Türker joined Dr. Sandra Encalada’s research group at The Scripps Research Institute, US as a postdoctoral research fellow. During her postdoctoral training, she was awarded the George E. Hewitt Foundation Fellowship for Medical Research. At Scripps, her work centered on identifying the functional impairments of the autophagy-lysosomal pathway and proteasome machinery in prion diseases.
In September 2024, Dr. Türker joined the Department of Molecular Biology and Genetics at Bilkent University as an Assistant Professor. Her group explores specialized protein degradation machineries that regulate neuronal signal transduction in the mammalian nervous system.