Unconventional secretory routes: direct protein export across the plasma membrane of mammalian cells

Traffic. 2005 Aug;6(8):607-14. doi: 10.1111/j.1600-0854.2005.00302.x.


The vast majority of extracellular proteins are exported from mammalian cells by the endoplasmic reticulum/Golgi-dependent secretory pathway. For poorly understood reasons, however, a heterogenous group of extracellular 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 translocating from the cytoplasm directly across the plasma membrane 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 proangiogenic 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens, Protozoan / metabolism
  • Cell Membrane / metabolism*
  • Cell Membrane / ultrastructure
  • Eukaryotic Cells / metabolism*
  • Exocytosis
  • Fibroblast Growth Factor 2 / metabolism
  • Humans
  • Membrane Transport Proteins / metabolism
  • Protein Conformation
  • Protein Transport
  • Proteins / metabolism*
  • Protozoan Proteins / metabolism


  • Antigens, Protozoan
  • HASPB protein, Leishmania
  • Membrane Transport Proteins
  • Proteins
  • Protozoan Proteins
  • Fibroblast Growth Factor 2