tailieunhanh - Báo cáo khoa học: The mystery of nonclassical protein secretion A current view on cargo proteins and potential export routes

Most of the examples of protein translocation across a membrane (such as the import of classical secretory proteins into the endoplasmic reticulum, import of proteins into mitochondria and peroxisomes, as well as protein import into and export from the nucleus), are understood in great detail. In striking contrast, the phenomenon of unconven-tional protein secretion (also known as nonclassical protein export or ER/Golgi-independent protein secretion) from eukaryotic cells was discoveredmore than 10 years ago and yet the molecular mechanism and the molecular identity of machinery components that mediate this process remain elusive. . | Eur. J. Biochem. 270 2109-2119 2003 FEBS 2003 doi REVIEW ARTICLE The mystery of nonclassical protein secretion A current view on cargo proteins and potential export routes Walter Nickel Biochemie-Zentrum Heidelberg University of Heidelberg Germany Most of the examples of protein translocation across a membrane such as the import of classical secretory proteins into the endoplasmic reticulum import of proteins into mitochondria and peroxisomes as well as protein import into and export from the nucleus are understood in great detail. In striking contrast the phenomenon of unconventional protein secretion also known as nonclassical protein export or ER Golgi-independent protein secretion from eukaryotic cells was discovered more than 10 years ago and yet the molecular mechanism and the molecular identity of machinery components that mediate this process remain elusive. This problem appears to be even more complex as several lines of evidence indicate that various kinds of mechanistically distinct nonclassical export routes may exist. In most cases these secretory mechanisms are gated in a tightly controlled fashion. This reviewaims to provide a comprehensive overview of our current knowledge as a basis for the development of new experimental stmeegies designed to unravel the molecular machineries mediating ER Golgi-independent protein secretion. Beyond solving a fundamental problem in current cell biology the molecular analysis of these processes is of major biomedical importance as these export routes are taken by proteins such as angiogenic growth factors inflammatory cytokines components of the extracellular matrix which regulate cell differentiation proliferation and apoptosis viral proteins and parasite surface proteins potentially involved in host infection. Keywords unconventional protein secretion nonclassical export protein targeting membrane translocation extracellular localization FGF-2 trafficking galectin trafficking .