Distinct Protein Sorting and Localization to Premelanosomes, Melanosomes, and Lysosomes in Pigmented Melanocytic Cells✪
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Melanosomes and premelanosomes are lysosome-related organelles with a unique structure and cohort of resident proteins. We have positioned these organelles relative to endosomes and lysosomes in pigmented melanoma cells and melanocytes. Melanosome resident proteins Pmel17 and TRP1 localized to separate vesicular structures that were distinct from those enriched in lysosomal proteins. In immunogold-labeled ultrathin cryosections, Pmel17 was most enriched along the intralumenal striations of premelanosomes. Increased pigmentation was accompanied by a decrease in Pmel17 and by an increase in TRP1 in the limiting membrane. Both proteins were largely excluded from lysosomal compartments enriched in LAMP1 and cathepsin D. By kinetic analysis of fluid phase uptake and immunogold labeling, premelanosomal proteins segregated from endocytic markers within an unusual endosomal compartment. This compartment contained Pmel17, was accessed by BSA–gold after 15 min, was acidic, and displayed a cytoplasmic planar coat that contained clathrin. Our results indicate that premelanosomes and melanosomes represent a distinct lineage of organelles, separable from conventional endosomes and lysosomes within pigmented cells. Furthermore, they implicate an unusual clathrin-coated endosomal compartment as a site from which proteins destined for premelanosomes and lysosomes are sorted.
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NCKX5 could play a role in maintaining local calcium concentrations in or near coated endosomes to facilitate membrane fusion and delivery of pmel17.
“We propose that NCKX5 could play a role in maintaining local calcium concentrations in or near to the coated endosomes, which are closely associated with the TGN (47), to facilitate appropriate membrane fusion”
From SLC24A5 encodes a trans-Golgi network protein with potassium-dependent sodium-calcium exchange activity that regulates human epidermal melanogenesis (2008) · cites this paper as [47]
Lamp1 is enriched in lysosomes.
“The 85-kDa form of pmel17 that is down-regulated by SLC24A5 knockdown is a marker of early melanosomes (25), whereas Lamp1 is enriched in lysosomes (47).”
From SLC24A5 encodes a trans-Golgi network protein with potassium-dependent sodium-calcium exchange activity that regulates human epidermal melanogenesis (2008) · cites this paper as [47]
In the model proposed by Raposo et al., the coated endosome serves as a critical sorting point between endocytic and pre-melanosomal pathways.
“In the model proposed by Raposo et al. (47,48), the coated endosome (also referred to as a stage 1 melanosome) serves as a critical sorting point between endocytic and pre-melanosomal pathways, from which macromolecules are specifically directed into melanosomal or lysosomal pathways.”
From SLC24A5 encodes a trans-Golgi network protein with potassium-dependent sodium-calcium exchange activity that regulates human epidermal melanogenesis (2008) · cites this paper as [47]
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Self-citationCell-specific ATP7A transport sustains copper-dependent tyrosinase activity in melanosomes
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PMEL : a pigment cell‐specific model for functional amyloid formation
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Self-citationSNX1 Defines an Early Endosomal Recycling Exit for Sortilin and Mannose 6‐Phosphate Receptors
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Self-citationProteomic Analysis of Early Melanosomes: Identification of Novel Melanosomal Proteins
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- Authors
- Raposo, G., Tenza, D., Murphy, D. M., Berson, J. F., & Marks, M. S.
- Affiliations
- aCurie Institute, Research Section, Paris, 7505 France
- University of Pennsylvania (US)
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2001-02-19
- Volume
- 152
- Issue
- 4
- Pages
- 809-824
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2195785
- OpenAlex
- W2106782182
- Cited by
- 451
- References
- 64
- Citations by year
- 2026: 4 · 2025: 17 · 2024: 17 · 2023: 15 · 2022: 17 · 2021: 23 · 2020: 19 · 2019: 13 · 2018: 21 · 2017: 25 · 2016: 11 · 2015: 13 · 2014: 14 · 2013: 21 · 2012: 12
- FWCI
- 8.04
- 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)
- Funders
- National Eye Institute (R01 EY 12207, R01EY012207)
- National Cancer Institute (T32CA009140, T32 CA 09140)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- premelanosomes, melanosomes, lysosomes, protein sorting, melanosome biogenesis, gp100, TRP-1, melanocytes, melanoma cells, pigmentation, LAMP1, cathepsin D, endosomes, organelle biogenesis
- MeSH terms
- Endocytosis, Lysosomes, Melanocytes, Membrane Glycoproteins, Models, Biological, Neoplasm Proteins, Proteins, Endosomes, Organelles, Lysosomal Storage Diseases, Melanosomes, Protein Transport, Protein Sorting Signals, Clathrin-Coated Vesicles, gp100 Melanoma Antigen
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