The ternary Rab27a-Myrip-Myosin VIIa complex regulates melanosome motility in the retinal pigment epithelium
Open accessAbstract
The retinal pigment epithelium (RPE) contains melanosomes similar to those found in the skin melanocytes, which undergo dramatic light-dependent movements in fish and amphibians. In mammals, those movements are more subtle and appear to be regulated by the Rab27a GTPase and the unconventional myosin, Myosin VIIa (MyoVIIa). Here we address the hypothesis that a recently identified Rab27a- and MyoVIIa-interacting protein, Myrip, promotes the formation of a functional tripartite complex. In heterologous cultured cells, all three proteins co-immunoprecipitated following overexpression. Rab27a and Myrip localize to the peripheral membrane of RPE melanosomes as observed by immunofluorescence and immunoelectron microscopy. Melanosome dynamics were studied using live-cell imaging of mouse RPE primary cultures. Wild-type RPE melanosomes exhibited either stationary or slow movement interrupted by bursts of fast movement, with a peripheral directionality trend. Nocodazole treatment led to melanosome paralysis, suggesting that movement requires microtubule motors. Significant and similar alterations in melanosome dynamics were observed when any one of the three components of the complex was missing, as studied in ashen- (Rab27a defective) and shaker-1 (MyoVIIa mutant)-derived RPE cells, and in wild-type RPE cells transduced with adenovirus carrying specific sequences to knockdown Myrip expression. We observed a significant increase in the number of motile melanosomes, exhibiting more frequent and prolonged bursts of fast movement, and inversion of directionality. Similar alterations were observed upon cytochalasin D treatment, suggesting that the Rab27a-Myrip-MyoVIIa complex regulates tethering of melanosomes onto actin filaments, a process that ensures melanosome movement towards the cell periphery.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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 Lopes et al., 2007
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 Lopes et al., 2007
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The Retinal Pigment Epithelium in Visual Function
Strauss, O. (2005) · Physiological Reviews · doi:10.1152/physrev.00021.2004 · Cited by 2,828 · see citing works
Self-citationSönnichsen, B., Renzis, S. D., Nielsen, E., Rietdorf, J., & Zerial, M. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.149.4.901 · Cited by 1,013 · see citing works
Kinesin and Dynein Move a Peroxisome in Vivo: A Tug-of-War or Coordinated Movement?
Kural, C., Kim, H., Syed, S., Goshima, G., Gelfand, V. I., & Selvin, P. R. (2005) · Science · doi:10.1126/science.1108408 · Cited by 607 · see citing works
The melanosome: membrane dynamics in black and white
Marks, M. S., & Seabra, M. C. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35096009 · Cited by 452 · see citing works
Self-citationWu, X., Bowers, B., Rao, K., Wei, Q., & Hammer, J. A. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.143.7.1899 · Cited by 419 · see citing works
Linking Albinism and Immunity: The Secrets of Secretory Lysosomes
Stinchcombe, J. C., Bossi, G., & Griffiths, G. M. (2004) · Science · doi:10.1126/science.1095291 · Cited by 361 · see citing works
A Family of Rab27-binding Proteins
Strom, M., Hume, A. N., Tarafder, A. K., Barkagianni, E., & Seabra, M. C. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202574200 · Cited by 324 · see citing works
Self-citationInteractions and regulation of molecular motors in Xenopus melanophores
Gross, S. P., Tuma, M. C., Deacon, S. W., Serpinskaya, A. S., Reilein, A. R., & Gelfand, V. I. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200105055 · Cited by 300 · see citing works
Controlling the location and activation of Rab GTPases
Seabra, M. C., & Wasmeier, C. (2004) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2004.06.014 · Cited by 289 · see citing works
Self-citationCoordination of opposite-polarity microtubule motors
Gross, S. P., Welte, M. A., Block, S. M., & Wieschaus, E. F. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200109047 · Cited by 280 · see citing works
Gibbs, D., Kitamoto, J., & Williams, D. S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1130432100 · Cited by 250 · see citing works
The Quest for the Mechanism of Melanin Transfer
Bossche, K. V. D., Naeyaert, J., & Lambert, J. (2006) · Traffic · doi:10.1111/j.1600-0854.2006.00425.x · Cited by 246 · see citing works
Rab27a enables myosin Va-dependent melanosome capture by recruiting the myosin to the organelle
Wu, X., Rao, K., Bowers, M., Copeland, N. G., Jenkins, N. A., & Hammer, J. A. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.6.1091 · Cited by 233 · see citing works
Deficient geranylgeranylation of Ram/Rab27 in choroideremia
Seabra, M. C., Ho, Y. K., & Anant, J. S. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.41.24420 · Cited by 223 · see citing works
Self-citationVersatile Role of Rab27 in Membrane Trafficking: Focus on the Rab27 Effector Families
Fukuda, M. (2005) · The Journal of Biochemistry · doi:10.1093/jb/mvi002 · Cited by 215 · see citing works
Kuroda, T. S., Fukuda, M., Ariga, H., & Mikoshiba, K. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m112414200 · Cited by 211 · see citing works
Transport of ER vesicles on actin filaments in neurons by myosin V
Tabb, J. S., Molyneaux, B. J., Cohen, D. L., Kuznetsov, S. A., & Langford, G. M. (1998) · Journal of Cell Science · doi:10.1242/jcs.111.21.3221 · Cited by 203 · see citing works
Rab GTPases and Myosin Motors in Organelle Motility
Seabra, M. C., & Coudrier, E. (2004) · Traffic · doi:10.1111/j.1398-9219.2004.00190.x · Cited by 199 · see citing works
Self-citationMyRIP, a novel Rab effector, enables myosin VIIa recruitment to retinal melanosomes
El‐Amraoui, A., Schonn, J., Küssel‐Andermann, P., Blanchard, S., Desnos, C., Henry, J., Wolfrum, U., Darchen, F., & Petit, C. (2002) · The EMBO Reports · doi:10.1093/embo-reports/kvf090 · Cited by 187 · see citing works
Rab27a Is an Essential Component of Melanosome Receptor for Myosin Va
Wu, X., Wang, F., Rao, K., Sellers, J. R., & Hammer, J. A. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.01-12-0595 · Cited by 172 · see citing works
Fukuda, M., & Kuroda, T. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203862200 · Cited by 169 · see citing works
Mutant myosin VIIa causes defective melanosome distribution in the RPE of shaker-1 mice
Liu, X., Ondek, B., & Williams, D. S. (1998) · Nature Genetics · doi:10.1038/470 · Cited by 168 · see citing works
Desnos, C., Schonn, J., Huet, S., Tran, V. S., El-Amraoui, A., Raposo, G., Fanget, I., Chapuis, C., Ménasché, G., Basile, G. D. S., et al. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200302157 · Cited by 168 · see citing works
The albino retina: an abnormality that provides insight into normal retinal development
Jeffery, G. (1997) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)10080-1 · Cited by 163 · see citing works
Pigment Cells: A Model for the Study of Organelle Transport
Nascimento, A. A. C., Roland, J. T., & Gelfand, V. I. (2003) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.19.111401.092937 · Cited by 159 · see citing works
Functional redundancy of Rab27 proteins and the pathogenesis of Griscelli syndrome
Barral, D. C., Ramalho, J. S., Anders, R., Hume, A. N., Knapton, H. J., Tolmachova, T., Collinson, L., Goulding, D., Authi, K. S., & Seabra, M. C. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15058 · Cited by 157 · see citing works
Self-citationFunctional redundancy of Rab27 proteins and the pathogenesis of Griscelli syndrome
Barral, D. C., Ramalho, J. S., Anders, R., Hume, A. N., Knapton, H. J., Tolmachova, T., Collinson, L., Goulding, D., Authi, K. S., & Seabra, M. C. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215058 · Cited by 155 · see citing works
Self-citationThe leaden Gene Product Is Required with Rab27a to Recruit Myosin Va to Melanosomes in Melanocytes
Hume, A. N., Collinson, L., Hopkins, C. R., Strom, M., Barral, D. C., Bossi, G., Griffiths, G. M., & Seabra, M. C. (2002) · Traffic · doi:10.1034/j.1600-0854.2002.030305.x · Cited by 154 · see citing works
Self-citationRole of myosin VIIa and Rab27a in the motility and localization of RPE melanosomes
Gibbs, D., Azarian, S. M., Lillo, C., Kitamoto, J., Klomp, A. E., Steel, K. P., Libby, R. T., & Williams, D. S. (2004) · Journal of Cell Science · doi:10.1242/jcs.01580 · Cited by 152 · see citing works
Bridgman, P. C. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.146.5.1045 · Cited by 151 · see citing works
Melanophilin, the Product of the Leaden Locus, is Required for Targeting of Myosin‐Va to Melanosomes
Provance, D. W., James, T. L., & Mercer, J. A. (2002) · Traffic · doi:10.1034/j.1600-0854.2002.030205.x · Cited by 133 · see citing works
Futter, C. E., Ramalho, J. S., Jaissle, G. B., Seeliger, M. W., & Seabra, M. C. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e03-10-0772 · Cited by 110 · see citing works
Self-citationHume, A. N., Tarafder, A. K., Ramalho, J. S., Sviderskaya, E. V., & Seabra, M. C. (2006) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-05-0457 · Cited by 91 · see citing works
Self-citationThe Globular Tail Domain of Myosin Va Functions as an Inhibitor of the Myosin Va Motor
Li, X., Jung, H. S., Mabuchi, K., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602957200 · Cited by 89 · see citing works
Culture of ratretinal pigment epithelium
Edwards, R. B. (1977) · In Vitro Cellular & Developmental Biology - Plant · doi:10.1007/bf02616175 · Cited by 73 · see citing works
Rab8 Regulates the Actin-based Movement of Melanosomes
Chabrillat, M. L., Wilhelm, C., Wasmeier, C., Sviderskaya, E. V., Louvard, D., & Coudrier, E. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-09-0770 · Cited by 65 · see citing works
Making Sense of Melanosome Dynamics in Mouse Melanocytes
Wu, X., & Hammer, J. A. (2000) · Pigment Cell Research · doi:10.1034/j.1600-0749.2000.130405.x · Cited by 57 · see citing works
The molecular regulation of organelle transport in mammalian retinal pigment epithelial cells
Futter, C. E. (2006) · Pigment Cell Research · doi:10.1111/j.1600-0749.2006.00303.x · Cited by 50 · see citing works
Self-citationThe unconventional myosin-VIIa associates with lysosomes
Soni, L. E., Warren, C. M., Bucci, C., Orten, D. J., & Hasson, T. (2005) · Cell Motility and the Cytoskeleton · doi:10.1002/cm.20080 · Cited by 49 · see citing works
Functional Analysis of Slac2-c/MyRIP as a Linker Protein between Melanosomes and Myosin VIIa*[boxs]
Kuroda, T. S., & Fukuda, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501465200 · Cited by 41 · see citing works
Voltage-dependent ion channels in the mouse RPE: Comparison with Norrie disease mice
Wollmann, G., Lenzner, S., Berger, W., Rosenthal, R., Karl, M., & Strauß, O. (2005) · Vision Research · doi:10.1016/j.visres.2005.08.030 · Cited by 26 · see citing works
Self-citationKing-Smith (1997) · doi:10.1002/(sici)1097-0169(1997)38:3
Flagged first, then by citations
Cited by
Sorted by citations
The cell biology of the retinal pigment epithelium
Lakkaraju, A., Umapathy, A., Tan, L. X., Daniele, L., Philp, N. J., Boesze-Battaglia, K., & Williams, D. S. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100846 · Cited by 422 · see citing works
Lysosome-related organelles: driving post-Golgi compartments into specialisation
Raposo, G., Marks, M. S., & Cutler, D. F. (2007) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2007.05.001 · Cited by 215 · see citing works
Usher syndrome: Animal models, retinal function of Usher proteins, and prospects for gene therapy
Williams, D. S. (2008) · Vision Research · doi:10.1016/j.visres.2007.08.015 · Cited by 188 · see citing works
Retinal gene therapy with a large MYO7A cDNA using adeno-associated virus
Lopes, V. S., Boye, S. E., Louie, C. M., Boye, S., Dyka, F., Chiodo, V, Fofo, H., Hauswirth, W. W., & Williams, D. S. (2013) · Gene Therapy · doi:10.1038/gt.2013.3 · Cited by 112 · see citing works
Self-citationMicrotubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis
Jiang, M., Esteve-Rudd, J., Lopes, V. S., Diemer, T., Lillo, C., Rump, A., & Williams, D. S. (2015) · Journal of Cell Biology · doi:10.1083/jcb.201410112 · Cited by 85 · see citing works
Self-citationBurgoyne, T., O'Connor, M. N., Seabra, M. C., Cutler, D. F., & Futter, C. E. (2015) · Journal of Cell Science · doi:10.1242/jcs.164400 · Cited by 68 · see citing works
Self-citation
- Authors
- Lopes, V. S., Ramalho, J. S., Owen, D. M., Karl, M. O., Strauss, O., Futter, C. E., & Seabra, M. C.
- Affiliations
- Imperial College London (GB)
- University Medical Center Hamburg-Eppendorf (DE)
- University College London (GB)
- Corresponding author
- Seabra, Miguel C.
- Venue
- Traffic
- Publisher
- Wiley
- Published
- 2007-03-26
- Volume
- 8
- Issue
- 5
- Pages
- 486-499
- ISSN
- 1398-9219 (ISSN-L)
- 1600-0854
- PMC
- PMC1920545
- OpenAlex
- W2151326094
- Cited by
- 95
- References
- 42
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 8 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 6 · 2014: 2 · 2013: 6 · 2012: 8
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Traffic (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (075498)
- Deutsche Forschungsgemeinschaft
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council
- 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 › Molecular Biology › Retinal Development and Disorders
- Keywords
- Rab27a, MYO7A, melanosomes, retinal pigment epithelium, microtubule motor proteins, F-actin, melanosome transport
- MeSH terms
- rab27 GTP-Binding Proteins, Myosin VIIa, Actins, Animals, Biological Transport, Cells, Cultured, Chlorocebus aethiops, Dyneins, Epithelial Cells, Mice, Inbred C57BL, Myosins, Pigment Epithelium of Eye, Protein Binding, Transfection, Cytochalasin D, Nocodazole, RNA, Antisense, Mice, Knockout, COS Cells, Melanosomes, rab GTP-Binding Proteins, Vesicular Transport Proteins, Immunoprecipitation, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
