Secretome

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The secretome is the set of proteins expressed by an organism and secreted into the extracellular space. In humans, this subset of the proteome encompasses 13-20% of all proteins, including cytokines, growth factors, extracellular matrix proteins and regulators, and shed receptors. The secretome of a specific tissue can be measured by mass spectrometry and its analysis constitutes a type of proteomics known as secretomics.

Contents

Definition

The term secretome was coined by Tjalsma and colleagues in 2004 to denote all the factors secreted by a cell, along with the secretory pathway constituents. [1] In 2010, this definition of secretome was revised to include only proteins secreted into the extracellular space. [2] Related concepts include the matrisome, which is the subset of the secretome that includes extracellular matrix proteins and their associated proteins; [3] the receptome, which includes all membrane receptors, [4] and the adhesome, which includes all proteins involved in cell adhesion. [5] [6]

Quantification

The secreted proteins in humans account for 13–20% of the entire proteome and include growth factors, chemokines, cytokines, adhesion molecules, proteases and shed receptors. [2] Human protein-coding genes (39%, 19613 genes [7] ) are predicted to have either a signal peptide and/or at least one transmembrane region suggesting active transport of the corresponding protein out of the cell (secretion) or location in one of the numerous membrane systems in the cell. Increasing evidence showed that, in addition to the protein cargo, non-protein components, such as lipid, micro-RNAs and messenger-RNA, could also be secreted by cells via both microvesicles (100–>1000 nm diameter) − shedding from the plasma membrane − and exosomes (30–150 nm diameter) − released via endosomal-exocytosis event. [8] Factors present in both these organelles accounts for up to 42% of the secretome and have been incorporated as the collective secretome. [9] There is a vast array of methodologies available to study cell secretomes of plant cells, mammalian cells, stem cells and cancer cells. [9]

See also

References

  1. Tjalsma, H.; Antelmann, H.; Jongbloed, J. D.H.; Braun, P. G.; Darmon, E.; Dorenbos, R.; Dubois, J.-Y. F.; Westers, H.; Zanen, G.; Quax, W. J.; Kuipers, O. P.; Bron, S.; Hecker, M.; van Dijl, J. M. (8 June 2004). "Proteomics of Protein Secretion by Bacillus subtilis: Separating the "Secrets" of the Secretome". Microbiology and Molecular Biology Reviews. 68 (2): 207–233. doi: 10.1128/MMBR.68.2.207-233.2004 . PMC   419921 . PMID   15187182.
  2. 1 2 Agrawal GK, Jwa NS, Lebrun MH, Job D, Rakwal R (February 2010). "Plant secretome: unlocking secrets of the secreted proteins". Proteomics. 10 (4): 799–827. doi:10.1002/pmic.200900514. PMID   19953550. S2CID   20647387.
  3. Hynes, R. O.; Naba, A. (21 September 2011). "Overview of the Matrisome--An Inventory of Extracellular Matrix Constituents and Functions". Cold Spring Harbor Perspectives in Biology. 4 (1) a004903. doi:10.1101/cshperspect.a004903. PMC   3249625 . PMID   21937732.
  4. Ben-Shlomo, I.; Yu Hsu, S.; Rauch, R.; Kowalski, H. W.; Hsueh, A. J. W. (17 June 2003). "Signaling Receptome: A Genomic and Evolutionary Perspective of Plasma Membrane Receptors Involved in Signal Transduction". Science Signaling. 2003 (187) re9. doi:10.1126/stke.2003.187.re9. PMID   12815191. S2CID   12803444.
  5. Zaidel-Bar, Ronen; Itzkovitz, Shalev; Ma'ayan, Avi; Iyengar, Ravi; Geiger, Benjamin (August 2007). "Functional atlas of the integrin adhesome". Nature Cell Biology. 9 (8): 858–867. doi:10.1038/ncb0807-858. PMC   2735470 . PMID   17671451.
  6. Horton, Edward R.; Byron, Adam; Askari, Janet A.; Ng, Daniel H. J.; Millon-Frémillon, Angélique; Robertson, Joseph; Koper, Ewa J.; Paul, Nikki R.; Warwood, Stacey; Knight, David; Humphries, Jonathan D.; Humphries, Martin J. (19 October 2015). "Definition of a consensus integrin adhesome and its dynamics during adhesion complex assembly and disassembly". Nature Cell Biology. 17 (12): 1577–1587. doi:10.1038/ncb3257. PMC   4663675 . PMID   26479319.
  7. Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, et al. (January 2015). "Proteomics. Tissue-based map of the human proteome". Science. 347 (6220) 1260419. doi:10.1126/science.1260419. PMID   25613900. S2CID   802377.
  8. Xu R, Greening DW, Zhu HJ, Takahashi N, Simpson RJ (April 2016). "Extracellular vesicle isolation and characterization: toward clinical application". The Journal of Clinical Investigation. 126 (4): 1152–62. doi:10.1172/JCI81129. PMC   4811150 . PMID   27035807.
  9. 1 2 Mukherjee P, Mani S (November 2013). "Methodologies to decipher the cell secretome". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1834 (11): 2226–32. doi:10.1016/j.bbapap.2013.01.022. PMC   3652893 . PMID   23376189.

Further reading