Role of Cytoplasmic Dynein in Perinuclear Aggregation of Phagocytosed Melanosomes and Supranuclear Melanin Cap Formation in Human Keratinocytes
Open accessAbstract
Cytoplasmic dynein is a microtubule-associated motor molecule involved in the retrograde transport of membrane-bound organelles. To determine whether the supranuclear melanin cap of transferred, phagocytosed melanosomes in keratinocytes is associated with cytoplasmic dynein, we performed immunofluorescent confocal microscopy on human keratinocytes in situ. We identified the intermediate chain of cytoplasmic dynein by immunoblotting and examined its distribution by confocal microscopy in relation to microtubules and melano-phagolysosomes in vitro. We also used antisense and sense oligonucleotides of the cytoplasmic dynein heavy chain 1 (Dyh1) and time-lapse and microscopy. The intermediate chain of cytoplasmic dynein was identified in extracts of human foreskin epidermis and in isolated human keratinocytes. The intermediate chain localized with the perinuclear melano-phagolysosomal aggregates in vitro and the supranuclear melanin cap in situ. Antisense oligonucleotides directed towards Dyh1 resulted in dispersal of the keratinocyte perinuclear melano-phagolysosomal aggregates after 24 to 48 h, whereas cells treated with diluent or sense oligonucleotides maintained tight perinuclear aggregates. Taken together, these findings indicate that in human keratinocytes, the retrograde microtubule motor cytoplasmic dynein mediates the perinuclear aggregation of phagocytosed melanosomes, participates in the formation of the supranuclear melanin cap or "microparasol" and serves as a mechanism to help protect the nucleus from ultraviolet-induced DNA damage.
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The intermediate chain of cytoplasmic dynein co-localizes with melanin both in cultured human keratinocytes and human skin explants.
“Regarding the molecular players involved in melanin polarization, prior studies have shown that the intermediate chain of cytoplasmic dynein co-localizes with melanin both in cultured human keratinocytes and human skin explants [ 12 ].”
From Melanin's Journey from Melanocytes to Keratinocytes: Uncovering the Molecular Mechanisms of Melanin Transfer and Processing (2023) · cites this paper as [12]
The Results report colocalization of the dynein intermediate chain with perinuclear melano-phagolysosomes in cultured human keratinocytes and with supranuclear pigment in human skin. However, the methods describe frozen sections of forearm skin, not skin explants; that specific experimental setting is not supported by our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredMelanin must be transferred to keratinocytes to exert its photoprotective function in these cells.
“Melanin must be transferred to keratinocytes to exert its photoprotective function in these cells.”
From Melanin's Journey from Melanocytes to Keratinocytes: Uncovering the Molecular Mechanisms of Melanin Transfer and Processing (2023) · cites this paper as [12]
Treatment with anti-sense DNA for cytoplasmic dynein heavy chain leads to a significant dispersion of perinuclear melanin in human keratinocytes.
“The same study also reported that treatment with anti-sense DNA for cytoplasmic dynein heavy chain leads to a significant dispersion of perinuclear melanin in human keratinocytes.”
From Melanin's Journey from Melanocytes to Keratinocytes: Uncovering the Molecular Mechanisms of Melanin Transfer and Processing (2023) · cites this paper as [12]
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- Authors
- Randolph Byers, H., Maheshwary, S., Amodeo, D. M., & Dykstra, S. G.
- Affiliations
- Boston University (US)
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2003-10
- Volume
- 121
- Issue
- 4
- Pages
- 813-820
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W1996513213
- Cited by
- 63
- References
- 77
- Citations by year
- 2026: 2 · 2025: 5 · 2023: 6 · 2022: 2 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 5 · 2017: 3 · 2016: 1 · 2015: 1 · 2013: 3 · 2012: 2
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- cytoplasmic dynein, dynein intermediate chain, melanosomes, phagocytosis, keratinocytes, retrograde transport, microtubule motor proteins, antisense oligonucleotides, UV-induced DNA damage, nuclear protection
- MeSH terms
- Cell Nucleus, Cells, Cultured, Cytoplasm, Dyneins, Humans, Melanocytes, Microtubules, Phagocytosis, Keratinocytes, Oligonucleotides, Antisense, Melanosomes
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