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Through the back door: Unconventional protein secretion.

Michael J Cohen1,2, William J Chirico3, Peter N Lipke1,2

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Eukaryotic cells secrete proteins via classical and unconventional pathways.
  • Classical secretion involves signal peptides for endoplasmic reticulum targeting.
  • Many proteins lacking signal peptides are also secreted actively, termed unconventionally secreted proteins.

Purpose of the Study:

  • To review fungal and metazoan unconventional secretory pathways.
  • To discuss the regulation of these pathways.
  • To propose criteria for identifying unconventional secretion mechanisms.

Main Methods:

  • Literature review of fungal and metazoan unconventional secretion.
  • Analysis of known unconventional secretory pathways.
  • Discussion of experimental approaches for identification.

Main Results:

  • Unconventionally secreted proteins lack signal peptides but are actively packaged.
  • These proteins have diverse extracellular functions, including cell signaling and immune modulation.
  • Identified pathways include direct plasma membrane transfer, microvesicle release, autophagy involvement, and endosomal routes.

Conclusions:

  • Unconventional secretion is a significant mechanism for protein release in eukaryotes.
  • These pathways are crucial for various cellular functions beyond the classical secretory system.
  • Further research is needed to fully elucidate and experimentally identify these secretion modes.