Role of myosin VIIa and Rab27a in the motility and localization of RPE melanosomes
Open accessAbstract
Myosin VIIa functions in the outer retina, and loss of this function causes human blindness in Usher syndrome type 1B (USH1B). In mice with mutant Myo7a, melanosomes in the retinal pigmented epithelium (RPE) are distributed abnormally. In this investigation we detected many proteins in RPE cells that could potentially participate in melanosome transport, but of those tested, only myosin VIIa and Rab27a were found to be required for normal distribution. Two other expressed proteins, melanophilin and myosin Va, both of which are required for normal melanosome distribution in melanocytes, were not required in RPE, despite the association of myosin Va with the RPE melanosome fraction. Both myosin VIIa and myosin Va were immunodetected broadly in sections of the RPE, overlapping with a region of apical filamentous actin. Some 70-80% of the myosin VIIa in RPE cells was detected on melanosome membranes by both subcellular fractionation of RPE cells and quantitative immunoelectron microscopy, consistent with a role for myosin VIIa in melanosome motility. Time-lapse microscopy of melanosomes in primary cultures of mouse RPE cells demonstrated that the melanosomes move in a saltatory manner, interrupting slow movements with short bursts of rapid movement (>1 RR01183m/second). In RPE cells from Myo7a-null mice, both the slow and rapid movements still occurred, except that more melanosomes underwent rapid movements, and each movement extended approximately five times longer (and further). Hence, our studies demonstrate the presence of many potential effectors of melanosome motility and localization in the RPE, with a specific requirement for Rab27a and myosin VIIa, which function by transporting and constraining melanosomes within a region of filamentous actin. The presence of two distinct melanosome velocities in both control and Myo7a-null RPE cells suggests the involvement of at least two motors other than myosin VIIa in melanosome motility, most probably, a microtubule motor and myosin Va.
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In cultures of mouse and human RPE cells, lack of myosin-7a results in inability to sequester melanosomes in the actin-rich apical domain; instead melanosomes undergo more rapid bidirectional movements along microtubules in the cell body.
“In cultures of mouse and human RPE cells, lack of myosin-7a results in the inability to sequester melanosomes in the actin-rich apical domain; instead the melanosomes undergo more rapid bidirectional movements along microtubules in the cell body (Gibbs et al., 2004, 2010; Lopes et al., 2007; Jiang et al., 2019).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Gibbs et al., 2004
Myosin-5a and myosin-7a have comparable roles in the motility of melanosomes; both capture melanosomes from microtubule transport.
“Myosin-5a and myosin-7a have comparable roles in the motility of melanosomes; both capture melanosomes from microtubule transport: myosin-5a in melanocytes (Wu et al., 1998) and myosin-7a in RPE cells (Gibbs et al., 2004; Lopes et al., 2007).”
From Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis (2015) · cites this paper as Gibbs 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 Gibbs et al., 2004
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References 59 · Cited by 152
Research works printed but not linked: 1
- Perkins BD, Matsui JI, Murphy MK, Dowling JE. Histological and physiological abnormalities in myosin VIIA mutant zebrafish. Invest. Ophthalmol. Vis. Sci. 2004;45:3591. [Google Scholar]
- Authors
- Gibbs, D., Azarian, S. M., Lillo, C., Kitamoto, J., Klomp, A. E., Steel, K. P., Libby, R. T., & Williams, D. S.
- Affiliations
- University of California San Diego (US)
- Departments of Pharmacology and Neurosciences, UCSD School of Medicine, La Jolla, CA 92093-0912, USA
- MRC Institute of Hearing Research (GB)
- Corresponding author
- Williams, David S.
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2004-12-15
- Volume
- 117
- Issue
- 26
- Pages
- 6473-6483
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- PMC
- PMC2942070
- OpenAlex
- W2086183541
- Cited by
- 152
- References
- 59
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 7 · 2023: 8 · 2022: 8 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 3 · 2017: 5 · 2016: 5 · 2015: 6 · 2014: 7 · 2013: 10 · 2012: 7
- FWCI
- 4.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institutes of Health (5p30ey012598-05)
- National Eye Institute (P30-EY012598, EY 12598, R01EY007042, EY07042)
- National Center for Research Resources (P40RR001183, RR 01183)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- MYO7A, Rab27a, retinal pigment epithelium, melanosomes, Usher syndrome type 1B, myosin Va, melanophilin, F-actin, melanosome transport, microtubule motor proteins
- MeSH terms
- Myosin VIIa, Animals, Cells, Cultured, Dyneins, Immunohistochemistry, Intracellular Membranes, Melanocytes, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Mutant Strains, Mutation, Myosins, Pigment Epithelium of Eye, Subcellular Fractions, Blotting, Western, Reverse Transcriptase Polymerase Chain Reaction, Melanosomes, rab GTP-Binding Proteins, Mice
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