Multiple roles for the actin cytoskeleton during regulated exocytosis
Open accessAbstract
Regulated exocytosis is the main mechanism utilized by specialized secretory cells to deliver molecules to the cell surface by virtue of membranous containers (i.e., secretory vesicles). The process involves a series of highly coordinated and sequential steps, which include the biogenesis of the vesicles, their delivery to the cell periphery, their fusion with the plasma membrane, and the release of their content into the extracellular space. Each of these steps is regulated by the actin cytoskeleton. In this review, we summarize the current knowledge regarding the involvement of actin and its associated molecules during each of the exocytic steps in vertebrates, and suggest that the overall role of the actin cytoskeleton during regulated exocytosis is linked to the architecture and the physiology of the secretory cells under examination. Specifically, in neurons, neuroendocrine, endocrine, and hematopoietic cells, which contain small secretory vesicles that undergo rapid exocytosis (on the order of milliseconds), the actin cytoskeleton plays a role in pre-fusion events, where it acts primarily as a functional barrier and facilitates docking. In exocrine and other secretory cells, which contain large secretory vesicles that undergo slow exocytosis (seconds to minutes), the actin cytoskeleton plays a role in post-fusion events, where it regulates the dynamics of the fusion pore, facilitates the integration of the vesicles into the plasma membrane, provides structural support, and promotes the expulsion of large cargo molecules.
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A dense ring of cortical branched actin below the cell membrane is a barrier that mechanically inhibits nonspecific vesicle fusion, thereby allowing for coordinated exocytosis.
“A dense ring of cortical branched actin below the cell membrane is a barrier that mechanically inhibits nonspecific vesicle fusion, thereby allowing for coordinated exocytosis (Fig. 1c) [11, 13, 21].”
From HEM1 Actin Immunodysregulatory Disorder: Genotypes, Phenotypes, and Future Directions (2022) · cites this paper as [11]
In “Anchoring site for the secretory vesicles and barrier function” (page unavailable), the review describes cortical actin as a thick meshwork and presents its physical-barrier role as a model; it also reports an actin ring at NK-cell fusion sites. The claim captures that proposed barrier role, but the paper does not identify the barrier as branched actin or establish a dense ring as its general structure. It also states the proposed mechanism more definitively than the review does. (LLM, conf=0.87)
Experimental — accuracy not yet measuredA dense ring of branched actin surrounds the cytosol, creating a barrier at the cell cortex that regulates vesicle secretion.
“Additionally, a dense ring of branched actin surrounds the cytosol, creating a barrier at the cell cortex that regulates vesicle secretion [11–13].”
From HEM1 Actin Immunodysregulatory Disorder: Genotypes, Phenotypes, and Future Directions (2022) · cites this paper as [11]
The 'Anchoring site for the secretory vesicles and barrier function' section (page unavailable) describes cortical actin as a thick meshwork that can act as a barrier between secretory vesicles and the plasma membrane. It does not describe that meshwork as branched or as a ring surrounding the cytosol; the actin ring it mentions is at an NK-cell immunological synapse and delimits an area of granule fusion. (LLM, conf=0.86)
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Cites
Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 Å resolution
Sutton, R. B., Fasshauer, D., Jahn, R., & Brunger, A. T. (1998) · Nature · doi:10.1038/26412 · Cited by 2,417 · cited 1× · see citing works
“Typically, three SNAREs are required to promote fusion, with one SNARE providing two helices (typically a SNAP protein) [85–87].”
BackgroundMunc18-1 Promotes Large Dense-Core Vesicle Docking
Voets, T., Toonen, R. F., Brian, E. C., de Wit, H., Moser, T., Rettig, J., Südhof, T. C., Neher, E., & Verhage, M. (2001) · Neuron · doi:10.1016/s0896-6273(01)00391-9 · Cited by 396 · cited 1× · see citing works
“Munc18-1 results in severe disruption of vesicles docking at the plasma membrane, as shown by electron microscopy [94, 95].”
BackgroundThe organization of cytoplasm at the presynaptic active zone of a central nervous system synapse
Landis, D. M. D., Hall, A. K., Weinstein, L. A., & Reese, T. S. (1988) · Neuron · doi:10.1016/0896-6273(88)90140-7 · Cited by 333 · see citing works
Minireview: How Peptide Hormone Vesicles Are Transported to the Secretion Site for Exocytosis
Park, J. J., & Loh, Y. P. (2008) · Molecular Endocrinology · doi:10.1210/me.2008-0209 · Cited by 81 · see citing works
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- Authors
- Porat-Shliom, N., Milberg, O., Masedunskas, A., & Weigert, R.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- University of North Carolina at Chapel Hill (US)
- National Institutes of Health (US)
- Corresponding author
- Weigert, Roberto
- Venue
- Cellular and Molecular Life Sciences
- Published
- 2012-09-18
- Volume
- 70
- Issue
- 12
- Pages
- 2099-2121
- ISSN
- 1420-682X (ISSN-L)
- 1420-9071
- PMC
- PMC4052552
- OpenAlex
- W1974714186
- Cited by
- 181
- References
- 4
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 5 · 2023: 9 · 2022: 12 · 2021: 12 · 2020: 16 · 2019: 15 · 2018: 21 · 2017: 18 · 2016: 18 · 2015: 15 · 2014: 16 · 2013: 9
- FWCI
- 1.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cellular and Molecular Life Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health (Z99 DE999999)
- National Institute of General Medical Sciences (T32GM008339)
- National Institute of Dental and Craniofacial Research (ZIADE000717)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
- Keywords
- actin cytoskeleton, regulated exocytosis, secretory vesicles, vesicle docking, fusion pore dynamics, exocytosis, neurons, neuroendocrine cells, endocrine cells, hematopoietic cells, cargo release
- MeSH terms
- Actins, Cytoskeleton, Exocytosis, Humans, Membrane Fusion, Models, Biological, Myosins, Secretory Vesicles, Secretory Pathway
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