Ca2+ and synaptotagmin VII–dependent delivery of lysosomal membrane to nascent phagosomes
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Synaptotagmin (Syt) VII is a ubiquitously expressed member of the Syt family of Ca2+ sensors. It is present on lysosomes in several cell types, where it regulates Ca2+-dependent exocytosis. Because [Ca2+]i and exocytosis have been associated with phagocytosis, we investigated the phagocytic ability of macrophages from Syt VII-/- mice. Syt VII-/- macrophages phagocytose normally at low particle/cell ratios but show a progressive inhibition in particle uptake under high load conditions. Complementation with Syt VII rescues this phenotype, but only when functional Ca2+-binding sites are retained. Reinforcing a role for Syt VII in Ca2+-dependent phagocytosis, particle uptake in Syt VII-/- macrophages is significantly less dependent on [Ca2+]i. Syt VII is concentrated on peripheral domains of lysosomal compartments, from where it is recruited to nascent phagosomes. Syt VII recruitment is rapidly followed by the delivery of Lamp1 to phagosomes, a process that is inhibited in Syt VII-/- macrophages. Thus, Syt VII regulates the Ca2+-dependent mobilization of lysosomes as a supplemental source of membrane during phagocytosis.
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Syts constitute a group of membrane proteins that regulate vesicle docking and fusion in processes such as exocytosis and phagocytosis.
“Syts constitute a group of membrane proteins that regulate vesicle docking and fusion in processes such as exocytosis (11, 23) and phagocytosis (11, 24, 25).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [24]
The Introduction describes synaptotagmins as a family of membrane proteins involved in exocytic membrane fusion, and reports a Syt VII–dependent component of phagocytosis. The Discussion likewise links Syt VII to rapid membrane fusion during phagosome formation. These passages do not establish that synaptotagmins regulate vesicle docking. (LLM, conf=0.84)
Experimental — accuracy not yet measuredCa2+-binding synaptotagmin VII, as well as synaptotagmins II and XI, are associated with phagosome formation and biogenesis including the link between phagosomes and lysosomes.
“In this context, the Ca2+-binding synaptotagmin VII, which is linked to VAMP7 function in exocytosis, as well as the synaptotagmins II and XI have also been associated with phagosome formation and biogenesis including the link between phagosomes and lysosomes (17–19).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [19]
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- Authors
- Czibener, C., Sherer, N. M., Becker, S. M., Pypaert, M., Hui, E., Chapman, E. R., Mothes, W., & Andrews, N. W.
- Affiliations
- 1Section of Microbial Pathogenesis and
- Yale University (US)
- Howard Hughes Medical Institute (US)
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2006-09-18
- Volume
- 174
- Issue
- 7
- Pages
- 997-1007
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2064391
- OpenAlex
- W2108594642
- Cited by
- 165
- References
- 58
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 6 · 2023: 8 · 2022: 12 · 2021: 15 · 2020: 7 · 2019: 6 · 2018: 8 · 2017: 5 · 2016: 13 · 2015: 10 · 2014: 10 · 2013: 5 · 2012: 6
- FWCI
- 3.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Institute of Mental Health (MH61876, R01MH061876)
- National Cancer Institute (R01CA098727)
- National Institute of General Medical Sciences (GM56827, R01GM056827, R01GM064625)
- National Institute of Allergy and Infectious Diseases (R37AI34867, R37AI034867)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- synaptotagmin VII, Ca2+ sensor, phagocytosis, macrophages, LAMP1
- MeSH terms
- Animals, Calcium, Cell Membrane, Cells, Cultured, Lysosomes, Macrophages, Phagocytosis, Phagosomes, Mice, Knockout, Synaptotagmins, Mice, Lysosomal Membrane Proteins, Lysosomal-Associated Membrane Protein 1
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