[2016 Spring Life Sciences & IBB Regular Seminar] ▶Subject: Unconventional Protein Secretion ▶Speaker: Min Goo Lee, MD, PhD. (Department of Pharmacology, Yonsei University College of Medicine) ▶Date: 4:00PM/Apr. 1(Fri.)/2016 ▶Place: Auditorium(1F), Postech Biotech Center *Abctract Most eukaryotic secretory or membrane proteins reach the plasma membrane through the conventional endoplasmic reticulum (ER)-Golgi pathway. However, evidence suggests that many cytoplasmic, nuclear, and signal-peptide-containing proteins also can reach the cell surface by unconventional trafficking pathways that bypass the Golgi. Recently, our group found that the selective activation of this unconventional trafficking pathway would be a potential therapeutic strategy for the treatment of diseases arising from the transport defects of misfolded proteins. Defective protein folding caused by genetic mutations is associated with wide spectrum of human diseases including cystic fibrosis (CF) and Pendred syndrome. The most prevalent CF-causing mutation of CFTR is the deletion of Phe508 (ΔF508), which leads to defects in the conventional Golgi-mediated exocytosis and cell surface expression. An integrated molecular and physiological analysis indicates that mechanisms associated with ER stress induce cell surface trafficking of ΔF508-CFTR via the alternative GRASP-dependent unconventional pathway. Furthermore, transgenic expression of GRASP55 in ΔF508-CFTR mice restored epithelial Cl- current and rescued mouse survival without apparent toxicity. Mutations in SLC26A4 cause non-syndromic recessive deafness with an enlarged vestibular aqueduct (DFNB4, [MIM 600791]) and Pendred syndrome (PDS, [MIM 274600]), and are considered to be the most common cause of hereditary hearing loss in East Asia. Specifically, p.H723R (His723Arg) is the most prevalent pathological mutation, and results in protein misfolding and defects of cell-surface trafficking. Interestingly, we recently have identified that cell-surface expression of a mutated form of pendrin can be restored by a DNAJC14-dependent unconventional secretion pathway. These findings offer a promising novel therapeutic target for the treatment of diseases caused by trafficking defects of misfolded proteins. ▶Inquiry: Prof. Youngsook Lee (279-2296) * This seminar will be given in English. please refrain from taking photos during seminars. *