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Cited by 110melanin and skin pigmentationRetinal Development and DisordersCellular transport and secretion

The role of Rab27a in the regulation of melanosome distribution within retinal pigment epithelial cells

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Futter, Clare E., Ramalho, José S., Jaissle, Gesine B., Seeliger, Mathias W., Seabra, Miguel C.·2004·Molecular Biology of the Cell
DOI 10.1091/mbc.e03-10-0772PMC PMC404021
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Abstract

Melanosomes within the retinal pigment epithelium (RPE) of mammals have long been thought to exhibit no movement in response to light, unlike fish and amphibian RPE. Here we show that the distribution of melanosomes within the mouse RPE undergoes modest but significant changes with the light cycle. Two hours after light onset, there is a threefold increase in the number of melanosomes in the apical processes that surround adjacent photoreceptors. In skin melanocytes, melanosomes are motile and evenly distributed throughout the cell periphery. This distribution is due to the interaction with the cortical actin cytoskeleton mediated by a tripartite complex of Rab27a, melanophilin, and myosin Va. In ashen (Rab27a null) mice RPE, melanosomes are unable to move beyond the adherens junction axis and do not enter apical processes, suggesting that Rab27a regulates melanosome distribution in the RPE. Unlike skin melanocytes, the effects of Rab27a are mediated through myosin VIIa in the RPE, as evidenced by the similar melanosome distribution phenotype observed in shaker-1 mice, defective in myosin VIIa. Rab27a and myosin VIIa are likely to be required for association with and movement through the apical actin cytoskeleton, which is a prerequisite for entry into the apical processes.

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Crossref · 10.1091/mbc.e03-10-0772

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  • Myosin-7a associates with RPE melanosomes by binding to MYRIP, which in turn binds to RAB27A on the melanosome surface.

    “myosin-7a associates with RPE melanosomes by binding to myosin-7a- and Rab-interacting protein (MYRIP) (El-Amraoui et al., 2002), which in turn binds to RAB27A on the melanosome surface (Futter et al., 2004; Gibbs et al., 2004; Kuroda and Fukuda, 2005; Klomp et al., 2007)”

    From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Futter et al., 2004

  • Melanosomes have been observed to move into the RPE apical processes in response to light onset.

    “Although more muted, melanosomes have been observed to move into the RPE apical processes in response to light onset (Futter et al., 2004).”

    From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Futter et al., 2004

  • Mutant CHM results in underprenylated RAB27A, which is the RAB that links myosin-7a to melanosomes.

    “Interestingly, mutant CHM results in underprenylated RAB27A (Seabra et al., 1995), which is the RAB that links myosin-7a to melanosomes (Futter et al., 2004; Gibbs et al., 2004).”

    From Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis (2015) · cites this paper as Futter et al., 2004

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Research works printed but not linked: 4

  1. Burnside, B., and Bost-Usinger, L. (1998). The retinal pigment epithelium cytoskeleton. In: The Retinal Pigment Epithelium: Function and Disease, eds. J.F. Marmor and T.J. Wolfensberger, Oxford, UK: Oxford University Press, 41–67.
  2. Burnside, B., and Laties, A.M. (1979). Pigment movement and cellular contractility in the retinal pigment epithelium. In: The Retinal Pigment Epithelium, eds. K.M. Zinn and M.F. Marmor, Cambridge, MA: Harvard University Press, 175–191.
  3. Petit, C. (2001). Usher syndrome: from genetics to pathogenesis. Annu. Rev. Genomics Hum. Genet. 2, 271–297. [DOI] [PubMed] [Google Scholar]
  4. van den Hurk, J.A. et al. (1997). Molecular basis of choroideremia (CHM): mutations involving the Rab escort protein-1 (REP-1) gene. Hum. Mutat. 9, 110–117. [DOI] [PubMed] [Google Scholar]

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Authors
Futter, C. E., Ramalho, J. S., Jaissle, G. B., Seeliger, M. W., & Seabra, M. C.
Affiliations
  • University College London (GB)
  • Centre of Ophthalmology, Biomedical Institute for Research in Light and Image, University of Coimbra, 3000-354 Coimbra, Portugal
  • University of Tübingen (DE)
  • Imperial College London (GB)
ORCID
Venue
Molecular Biology of the Cell
Publisher
American Society for Cell Biology (ASCB)
Published
2004-05
Volume
15
Issue
5
Pages
2264-2275
ISSN
  • 1059-1524 (ISSN-L)
  • 1939-4586
DOI
10.1091/mbc.e03-10-0772
PMC
PMC404021
OpenAlex
W2121707887
Cited by
110
References
39
Citations by year
2026: 1 · 2025: 4 · 2024: 5 · 2023: 8 · 2022: 5 · 2021: 3 · 2020: 9 · 2019: 8 · 2018: 4 · 2017: 1 · 2016: 4 · 2015: 7 · 2014: 3 · 2013: 3 · 2012: 2
FWCI
3.57
Type
journal article
Language
en
Open access
Locations
  • Molecular Biology of the Cell (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • Foundation Fighting Blindness
  • Wellcome Trust
  • Deutsche Forschungsgemeinschaft
  • Moorfields Eye Hospital NHS Foundation Trust
  • Medical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
Rab27a, melanosomes, retinal pigment epithelium, MYO7A, myosin Va, melanophilin, cortical actin cytoskeleton, light regulation, adherens junctions, apical processes, melanosome transport
MeSH terms
rab27 GTP-Binding Proteins, Animals, Cytoskeletal Proteins, Electrophysiology, Mice, Mutant Strains, Microscopy, Pigment Epithelium of Eye, Retina, Melanosomes, rab GTP-Binding Proteins, Mice

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