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Regulated secretion from hemopoietic cells.

Stinchcombe JC, Griffiths GM - J. Cell Biol. (1999)

View Article: PubMed Central - PubMed

Affiliation: Sir William Dunn School of Pathology, University of Oxford, OX1 3RE United Kingdom.

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For example, T lymphocytes use regulated secretion to selectively destroy appropriate targets recognized by the T cell receptor, while mast cells degranulate in response to IgE cross-linking to counter parasitic infection... Unlike conventional secretory cells (e.g., exocrine and endocrine cells) which use a separate organelle for the storage and release of their secretory products (Fig. 1 a), cells of the hemopoietic lineage use lysosomes to store and release their secretory products (Fig. 1 b; Griffiths 1996)... Since MHC class II presents peptides from extracellular pathogens that need to be taken up and degraded by the cell, the exocytosis of a compartment from the degradative pathway on the way to the lysosome is therefore ideal for efficient antigen presentation... Curiously, secretion of this multivesicular compartment not only translocates proteins of the outer membrane to the cell surface but also results in the release of small internal vesicles, termed exosomes, which may themselves have important biological effects (Zitvogel et al. 1998)... Several of the key proteins involved in secretion of conventional secretory granules are found in cells with secretory lysosomes... For example, both v- and t-SNARES (Brumell et al. 1995; Guo et al. 1998), as well as Rab proteins (Tardieux et al. 1992) and synaptotagmins (Baram et al. 1999), have been found to be associated with secretory lysosomes in hemopoietic cells (Table )... The sequences predict homologous cytosolic proteins of ∼400 kD... The gene is expressed in the majority of tissues examined, consistent with the abnormally sized lysosomes found in all CHS cell types... The HPS1 sequence provides few clues as to the function of this protein and there is no significant homology to other known proteins... The other protein that has been found to be defective is the adaptor protein AP3... Although secretory lysosomes are predominantly used by cells of the hemopoietic lineage, there are clearly some nonhemopoietic cells which use a lysosomal compartment for regulated secretion, such as melanocytes (Orlow 1995) and renal tubular cells (Swank et al. 1998)... If this is the case, then it is likely that the specialized secretory granules used for regulated secretion from exocrine and endocrine cells are a later evolutionary development... Intriguingly, although conventional endocrine and exocrine secretory cells contain distinct lysosomes and secretory storage compartments they contain a post-Golgi intermediate, the immature granule, on the pathway to these distinct organelles in which the newly synthesized secretory and lysosomal proteins coexist (Klumperman et al. 1998; Kuliawat et al. 1997).

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(a) Conventional secretory cells contain separate lysosomes and secretory granules. PC12 cells were transfected with the lysosomal protein CD63, tagged with GFP and costained with an antibody to secretogranin II, a secretory granule protein, in red. No overlap of the two compartments is observed. (b) Cells with secretory lysosomes package both lysosomal proteins and secretory proteins in the same compartment. A cytotoxic T lymphocyte is costained with the lysosomal membrane protein LAMP-2 (red) and the soluble secreted protein granzyme A (green). Extensive overlap of the two markers demonstrates colocalization in the same organelle (yellow).
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Figure 1: (a) Conventional secretory cells contain separate lysosomes and secretory granules. PC12 cells were transfected with the lysosomal protein CD63, tagged with GFP and costained with an antibody to secretogranin II, a secretory granule protein, in red. No overlap of the two compartments is observed. (b) Cells with secretory lysosomes package both lysosomal proteins and secretory proteins in the same compartment. A cytotoxic T lymphocyte is costained with the lysosomal membrane protein LAMP-2 (red) and the soluble secreted protein granzyme A (green). Extensive overlap of the two markers demonstrates colocalization in the same organelle (yellow).

Mentions: The process of regulated secretion (reviewed in Bugress and Kelly, 1987) is critical for the correct biological functioning of many different cells of the immune system, most of which are derived from the hemopoietic lineage (Table ). For example, T lymphocytes use regulated secretion to selectively destroy appropriate targets recognized by the T cell receptor, while mast cells degranulate in response to IgE cross-linking to counter parasitic infection. Unlike conventional secretory cells (e.g., exocrine and endocrine cells) which use a separate organelle for the storage and release of their secretory products (Fig. 1 a), cells of the hemopoietic lineage use lysosomes to store and release their secretory products (Fig. 1 b; Griffiths 1996). These organelles have been termed secretory lysosomes. Although the lysosomal nature of the secretory granules found in several hemopoietic cells has been known for many years, recent evidence supports the idea that secretory lysosomes may use specialized mechanisms for sorting and secretion, which differ from those found in conventional secretory cells. Interestingly, a small number of nonhemopoietic cells also use these mechanisms, suggesting that secretory lysosomes may represent an early form of regulated secretion.


Regulated secretion from hemopoietic cells.

Stinchcombe JC, Griffiths GM - J. Cell Biol. (1999)

(a) Conventional secretory cells contain separate lysosomes and secretory granules. PC12 cells were transfected with the lysosomal protein CD63, tagged with GFP and costained with an antibody to secretogranin II, a secretory granule protein, in red. No overlap of the two compartments is observed. (b) Cells with secretory lysosomes package both lysosomal proteins and secretory proteins in the same compartment. A cytotoxic T lymphocyte is costained with the lysosomal membrane protein LAMP-2 (red) and the soluble secreted protein granzyme A (green). Extensive overlap of the two markers demonstrates colocalization in the same organelle (yellow).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2164988&req=5

Figure 1: (a) Conventional secretory cells contain separate lysosomes and secretory granules. PC12 cells were transfected with the lysosomal protein CD63, tagged with GFP and costained with an antibody to secretogranin II, a secretory granule protein, in red. No overlap of the two compartments is observed. (b) Cells with secretory lysosomes package both lysosomal proteins and secretory proteins in the same compartment. A cytotoxic T lymphocyte is costained with the lysosomal membrane protein LAMP-2 (red) and the soluble secreted protein granzyme A (green). Extensive overlap of the two markers demonstrates colocalization in the same organelle (yellow).
Mentions: The process of regulated secretion (reviewed in Bugress and Kelly, 1987) is critical for the correct biological functioning of many different cells of the immune system, most of which are derived from the hemopoietic lineage (Table ). For example, T lymphocytes use regulated secretion to selectively destroy appropriate targets recognized by the T cell receptor, while mast cells degranulate in response to IgE cross-linking to counter parasitic infection. Unlike conventional secretory cells (e.g., exocrine and endocrine cells) which use a separate organelle for the storage and release of their secretory products (Fig. 1 a), cells of the hemopoietic lineage use lysosomes to store and release their secretory products (Fig. 1 b; Griffiths 1996). These organelles have been termed secretory lysosomes. Although the lysosomal nature of the secretory granules found in several hemopoietic cells has been known for many years, recent evidence supports the idea that secretory lysosomes may use specialized mechanisms for sorting and secretion, which differ from those found in conventional secretory cells. Interestingly, a small number of nonhemopoietic cells also use these mechanisms, suggesting that secretory lysosomes may represent an early form of regulated secretion.

View Article: PubMed Central - PubMed

Affiliation: Sir William Dunn School of Pathology, University of Oxford, OX1 3RE United Kingdom.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

For example, T lymphocytes use regulated secretion to selectively destroy appropriate targets recognized by the T cell receptor, while mast cells degranulate in response to IgE cross-linking to counter parasitic infection... Unlike conventional secretory cells (e.g., exocrine and endocrine cells) which use a separate organelle for the storage and release of their secretory products (Fig. 1 a), cells of the hemopoietic lineage use lysosomes to store and release their secretory products (Fig. 1 b; Griffiths 1996)... Since MHC class II presents peptides from extracellular pathogens that need to be taken up and degraded by the cell, the exocytosis of a compartment from the degradative pathway on the way to the lysosome is therefore ideal for efficient antigen presentation... Curiously, secretion of this multivesicular compartment not only translocates proteins of the outer membrane to the cell surface but also results in the release of small internal vesicles, termed exosomes, which may themselves have important biological effects (Zitvogel et al. 1998)... Several of the key proteins involved in secretion of conventional secretory granules are found in cells with secretory lysosomes... For example, both v- and t-SNARES (Brumell et al. 1995; Guo et al. 1998), as well as Rab proteins (Tardieux et al. 1992) and synaptotagmins (Baram et al. 1999), have been found to be associated with secretory lysosomes in hemopoietic cells (Table )... The sequences predict homologous cytosolic proteins of ∼400 kD... The gene is expressed in the majority of tissues examined, consistent with the abnormally sized lysosomes found in all CHS cell types... The HPS1 sequence provides few clues as to the function of this protein and there is no significant homology to other known proteins... The other protein that has been found to be defective is the adaptor protein AP3... Although secretory lysosomes are predominantly used by cells of the hemopoietic lineage, there are clearly some nonhemopoietic cells which use a lysosomal compartment for regulated secretion, such as melanocytes (Orlow 1995) and renal tubular cells (Swank et al. 1998)... If this is the case, then it is likely that the specialized secretory granules used for regulated secretion from exocrine and endocrine cells are a later evolutionary development... Intriguingly, although conventional endocrine and exocrine secretory cells contain distinct lysosomes and secretory storage compartments they contain a post-Golgi intermediate, the immature granule, on the pathway to these distinct organelles in which the newly synthesized secretory and lysosomal proteins coexist (Klumperman et al. 1998; Kuliawat et al. 1997).

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