Review Unconventional Secretory Routes: Direct Protein Export Across the Plasma Membrane of Mammalian Cells

The vast majority of extracellular proteins are exported from mammalian cells by the endoplasmic reticulum/ Golgi-dependent secretory pathway. For poorly under-stood reasons, however, a heterogenous group of extra-cellular proteins has been discovered that does not make use of signal peptide-dependent secretory transport. Both the release mechanisms and the molecular identity of the secretory machines involved have remained elusive. Recent studies now have established a subgroup of unconventional secretory proteins capable of translocat-ing from the cytoplasm directly across the plasma mem-brane to get access to the exterior of eukaryotic cells. This review aims to focus on a detailed comparison of the subcellular site of membrane translocation of various unconventional secretory proteins such as the proangio-genic molecule fibroblast growth factor-2 (FGF-2) and Leishmania hydrophilic acylated surface protein B (HASP B). A potential link between membrane translocation and quality control as an integral part of unconventional secretory processes is discussed. Key words: FGF-1, FGF-2, fibroblast growth factor, galec-tin, galectin-1, HASPB, hydrophilic acylated surface protein, membrane translocation, non-classical protein export, protein targeting, unconventional protein secretio