Macropinosome

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Macropinosomes are a type of cellular compartment that form as a result of macropinocytosis.

Function[edit]

Macropinosomes serve primarily in the uptake of solutes from the extracellular fluid.[1][2] Once inside the cell, macropinosomes undergo a process of maturation characterized by increasing expression of Rab7 as they progress through the endocytic pathway, until they fuse with lysosomes where the contents of the macropinosome are degraded.[3]

Regulation[edit]

PI3K and phosphoinositide phospholipase C activation have been shown to be necessary for macropinosome formation in fibroblasts.[4] Members of the SNX family have also been shown to be important in macropinosome formation.[5] Conversely, cyclic AMP has been shown to promote regurgitation from macropinosomes.[6]

Role in pathogenesis[edit]

Because the process of macropinocytosis is non-specific, many pathogens take advantage of macropinosomes to infect their target cells. One example is ebola, responsible for the devastating eponymous disease, which stimulates macropinosome formation upon binding to the target cell surface.[7] Shiga toxin produced by enterohemorrhagic E. coli has been shown to enter target cells via macropinocytosis, causing gastrointestinal tract complications.[8] Other pathogens that have been shown to utilize this mechanism are KSHV[9] and Salmonella.[10]

References[edit]

  1. ^ Racoosin, E. L.; Swanson, J. A. (1992). "M-CSF-induced macropinocytosis increases solute endocytosis but not receptor-mediated endocytosis in mouse macrophages". Journal of Cell Science 102 (4): 867–880. PMID 1429898.  edit
  2. ^ Hacker, U.; Albrecht, R.; Maniak, M. (1997). "Fluid-phase uptake by macropinocytosis in Dictyostelium". Journal of Cell Science 110 (2): 105–112. PMID 9044041.  edit
  3. ^ Racoosin, E. L.; Swanson, J. A. (1993). "Macropinosome maturation and fusion with tubular lysosomes in macrophages". The Journal of Cell Biology 121 (5): 1011–1020. PMC 2119679. PMID 8099075.  edit
  4. ^ Amyere, M.; Payrastre, B.; Krause, U.; Van Der Smissen, P.; Veithen, A.; Courtoy, P. J. (2000). "Constitutive Macropinocytosis in Oncogene-transformed Fibroblasts Depends on Sequential Permanent Activation of Phosphoinositide 3-Kinase and Phospholipase C". Molecular Biology of the Cell 11 (10): 3453–3467. PMC 15006. PMID 11029048.  edit
  5. ^ Wang, J. T. H.; Kerr, M. C.; Karunaratne, S.; Jeanes, A.; Yap, A. S.; Teasdale, R. D. (2010). "The SNX-PX-BAR Family in Macropinocytosis: The Regulation of Macropinosome Formation by SNX-PX-BAR Proteins". In Caplan, Steve H. PLoS ONE 5 (10): e13763. doi:10.1371/journal.pone.0013763. PMC 2966440. PMID 21048941.  edit
  6. ^ Veithen, A.; Amyere, M.; Van Der Smissen, P.; Cupers, P.; Courtoy, P. J. (1998). "Regulation of macropinocytosis in v-Src-transformed fibroblasts: Cyclic AMP selectively promotes regurgitation of macropinosomes". Journal of Cell Science 111 (16): 2329–2335. PMID 9683628.  edit
  7. ^ Saeed, M. F.; Kolokoltsov, A. A.; Albrecht, T.; Davey, R. A. (2010). "Cellular Entry of Ebola Virus Involves Uptake by a Macropinocytosis-Like Mechanism and Subsequent Trafficking through Early and Late Endosomes". In Basler, Christopher F. PLoS Pathogens 6 (9): e1001110. doi:10.1371/journal.ppat.1001110. PMC 2940741. PMID 20862315.  edit
  8. ^ Lukyanenko, V.; Malyukova, I.; Hubbard, A.; Delannoy, M.; Boedeker, E.; Zhu, C.; Cebotaru, L.; Kovbasnjuk, O. (2011). "Enterohemorrhagic Escherichia coli infection stimulates Shiga toxin 1 macropinocytosis and transcytosis across intestinal epithelial cells". AJP: Cell Physiology 301 (5): C1140–C1149. doi:10.1152/ajpcell.00036.2011. PMC 3213915. PMID 21832249.  edit
  9. ^ Valiya Veettil, M.; Sadagopan, S.; Kerur, N.; Chakraborty, S.; Chandran, B. (2010). "Interaction of c-Cbl with Myosin IIA Regulates Bleb Associated Macropinocytosis of Kaposi's Sarcoma-Associated Herpesvirus". In Früh, Klaus. PLoS Pathogens 6 (12): e1001238. doi:10.1371/journal.ppat.1001238. PMC 3009604. PMID 21203488.  edit
  10. ^ Kerr, M. C.; Wang, J. T. H.; Castro, N. A.; Hamilton, N. A.; Town, L.; Brown, D. L.; Meunier, F. A.; Brown, N. F.; Stow, J. L.; Teasdale, R. D. (2010). "Inhibition of the PtdIns(5) kinase PIKfyve disrupts intracellular replication of Salmonella". The EMBO Journal 29 (8): 1331–1347. doi:10.1038/emboj.2010.28. PMC 2868569. PMID 20300065.  edit