Secretion from Myeloid Cells: Secretory Lysosomes
- Author: Gillian M. Griffiths1
- Editor: Siamon Gordon2
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VIEW AFFILIATIONS HIDE AFFILIATIONSAffiliations: 1: Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Cambridge CB2 0XY, United Kingdom; 2: Oxford University, Oxford, United Kingdom
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Received 03 March 2016 Accepted 15 March 2016 Published 29 July 2016
- Correspondence: Gillian M. Griffiths, [email protected]

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Abstract:
Many cells of the myeloid lineage use an unusual secretory organelle to deliver their effector mechanisms. In these cells, the lysosomal compartment is often modified not only to fulfill the degradative functions of a lysosome but also as a mechanism for secreting additional proteins that are found in the lysosomes of each specialized cell type. These extra proteins vary from one cell type to another according to the specialized function of the cell. For example, mast cells package histamine; cytotoxic T cells express perforin; azurophilic granules in neutrophils express antimicrobial peptides, and platelets von Willebrand factor. Upon release, these very different proteins can trigger inflammation, cell lysis, microbial death, and clotting, respectively, and hence deliver the very different effector mechanisms of these different myeloid cells.
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Citation: Griffiths G. 2016. Secretion from Myeloid Cells: Secretory Lysosomes. Microbiol Spectrum 4(4):MCHD-0030-2016. doi:10.1128/microbiolspec.MCHD-0030-2016.




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Abstract:
Many cells of the myeloid lineage use an unusual secretory organelle to deliver their effector mechanisms. In these cells, the lysosomal compartment is often modified not only to fulfill the degradative functions of a lysosome but also as a mechanism for secreting additional proteins that are found in the lysosomes of each specialized cell type. These extra proteins vary from one cell type to another according to the specialized function of the cell. For example, mast cells package histamine; cytotoxic T cells express perforin; azurophilic granules in neutrophils express antimicrobial peptides, and platelets von Willebrand factor. Upon release, these very different proteins can trigger inflammation, cell lysis, microbial death, and clotting, respectively, and hence deliver the very different effector mechanisms of these different myeloid cells.

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Figures
Rab27a interacts with different effector proteins to provide different modes of secretion. (Left) In melanosomes, Rab27a interacts with the Slp melanophilin (Mlph), which in turn interacts with myosin (Myo) Va and captures melanosomes onto cortical actin at the plus ends of microtubules. (Right) In CTLs, Rab27a interacts with Munc13-4 on secretory lysosomes and also interacts with Slp1 to -3, which are localized to the plasma membrane.

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FIGURE 1
Rab27a interacts with different effector proteins to provide different modes of secretion. (Left) In melanosomes, Rab27a interacts with the Slp melanophilin (Mlph), which in turn interacts with myosin (Myo) Va and captures melanosomes onto cortical actin at the plus ends of microtubules. (Right) In CTLs, Rab27a interacts with Munc13-4 on secretory lysosomes and also interacts with Slp1 to -3, which are localized to the plasma membrane.
Secretory lysosomes are delivered to an area of plasma membrane depleted in cortical actin. CTLs expressing actin-green fluorescent protein (green), fixed and stained with CD63 (red), forming a synapse viewed from the side and en face. Reprinted from reference ( 11 ), with permission.

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FIGURE 2
Secretory lysosomes are delivered to an area of plasma membrane depleted in cortical actin. CTLs expressing actin-green fluorescent protein (green), fixed and stained with CD63 (red), forming a synapse viewed from the side and en face. Reprinted from reference ( 11 ), with permission.
Naive CD8 T cells express only low levels of Rac1 and no secretory lysosomes, Upon activation, TCR signaling triggers secretory lysosome biogenesis and prearms the CTL to kill. TCR signaling also activates Hh signaling, increasing levels of Rac1, required for actin reorganization and microtubule organization and thereby secretory lysosome polarization and release.

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FIGURE 3
Naive CD8 T cells express only low levels of Rac1 and no secretory lysosomes, Upon activation, TCR signaling triggers secretory lysosome biogenesis and prearms the CTL to kill. TCR signaling also activates Hh signaling, increasing levels of Rac1, required for actin reorganization and microtubule organization and thereby secretory lysosome polarization and release.
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