Myosin-Va and dynamic actin oppose microtubules to drive long-range organelle transport

Evans, Richard D.; Robinson, Christopher; Briggs, Deborah A.; Tooth, David J.; Ramalho, Jose S.; Cantero, Marta; Montoliu, Lluis; Patel, Shyamal; Sviderskaya, Elena V.; Hume, Alistair N.

doi:10.1016/j.cub.2014.06.019

A time-resolved Förster resonance energy transfer assay to investigate inhibitor binding to ABCG2 (2023)
Preprint / Working Paper
Mitchell-White, J. I., Briggs, D. A., Mistry, S. J., Mbiwan, H. A., Kellam, B., Holliday, N. D., Briddon, S. J., & Kerr, I. D. A time-resolved Förster resonance energy transfer assay to investigate inhibitor binding to ABCG2

The human ATP-binding cassette (ABC) transporter, ABCG2 is responsible for multidrug resistance in some tumours. Detailed knowledge of its activity is crucial for understanding drug transport and resistance in cancer, and has implications for wider p... Read More about A time-resolved Förster resonance energy transfer assay to investigate inhibitor binding to ABCG2.

Vinca alkaloid binding to P-glycoprotein occurs in a processive manner (2022)
Journal Article
Iqbal, S., Flux, C., Briggs, D. A., Deplazes, E., Long, J., Skrzypek, R., Rothnie, A., Kerr, I. D., & Callaghan, R. (2022). Vinca alkaloid binding to P-glycoprotein occurs in a processive manner. BBA - Biomembranes, 1864(10), Article 184005. https://doi.org/10.1016/j.bbamem.2022.184005

A mechanistic understanding of how P-glycoprotein (Pgp) is able to bind and transport its astonishing range of substrates remains elusive. Pharmacological data demonstrated the presence of at least four distinct binding sites, but their locations hav... Read More about Vinca alkaloid binding to P-glycoprotein occurs in a processive manner.

Rab27a co-ordinates actin-dependent transport by controlling organelle-associated motors and track assembly proteins (2020)
Journal Article
Alzahofi, N., Welz, T., Robinson, C. L., Page, E. L., Briggs, D. A., Stainthorp, A. K., Reekes, J., Elbe, D. A., Straub, F., Kallemeijn, W. W., Tate, E. W., Goff, P. S., Sviderskaya, E. V., Cantero, M., Montoliu, L., Nedelec, F., Miles, A. K., Bailly, M., Kerkhoff, E., & Hume, A. N. (2020). Rab27a co-ordinates actin-dependent transport by controlling organelle-associated motors and track assembly proteins. Nature Communications, 11(1), Article 3495. https://doi.org/10.1038/s41467-020-17212-6

© 2020, The Author(s). Cell biologists generally consider that microtubules and actin play complementary roles in long- and short-distance transport in animal cells. On the contrary, using melanosomes of melanocytes as a model, we recently discovered... Read More about Rab27a co-ordinates actin-dependent transport by controlling organelle-associated motors and track assembly proteins.

Application of fluorescence correlation spectroscopy to study substrate binding in styrene maleic acid lipid copolymer encapsulated ABCG2 (2020)
Journal Article
Horsey, A. J., Briggs, D. A., Holliday, N. D., Briddon, S. J., & Kerr, I. D. (2020). Application of fluorescence correlation spectroscopy to study substrate binding in styrene maleic acid lipid copolymer encapsulated ABCG2. BBA - Biomembranes, 1862(6), Article 183218. https://doi.org/10.1016/j.bbamem.2020.183218

© 2020 The Authors ABCG2 is one of a trio of human ATP binding cassette transporters that have the ability to bind and transport a diverse array of chemical substrates out of cells. This so-called “multidrug” transport has numerous physiological cons... Read More about Application of fluorescence correlation spectroscopy to study substrate binding in styrene maleic acid lipid copolymer encapsulated ABCG2.

Disruption of the Unique ABCG-Family NBD:NBD Interface Impacts Both Drug Transport and ATP Hydrolysis (2020)
Journal Article
Kapoor, P., Briggs, D. A., Cox, M. H., & Kerr, I. D. (2020). Disruption of the Unique ABCG-Family NBD:NBD Interface Impacts Both Drug Transport and ATP Hydrolysis. International Journal of Molecular Sciences, 21(3), Article 759. https://doi.org/10.3390/ijms21030759

ABCG2 is one of a triumvirate of human multidrug ATP binding cassette (ABC) transporters that are implicated in defense of cells and tissues against cytotoxic chemicals, but which can confer chemotherapy resistance states in oncology. Understanding t... Read More about Disruption of the Unique ABCG-Family NBD:NBD Interface Impacts Both Drug Transport and ATP Hydrolysis.

Nucleotide exchange factor Rab3GEP requires DENN and non-DENN elements for activation and targeting of Rab27a (2019)
Journal Article
Sanzà, P., Evans, R. D., Briggs, D. A., Cantero, M., Montoliu, L., Patel, S., Sviderskaya, E. V., Itzen, A., Figueiredo, A. C., Seabra, M. C., & Hume, A. N. (2019). Nucleotide exchange factor Rab3GEP requires DENN and non-DENN elements for activation and targeting of Rab27a. Journal of Cell Science, 132(9), 1-8. https://doi.org/10.1242/jcs.212035

Rab GTPases are compartment-specific molecular switches that regulate intracellular vesicular transport in eukaryotes. GDP/GTP exchange factors (GEFs) control Rab activation, and current models propose that localised and regulated GEF activity is imp... Read More about Nucleotide exchange factor Rab3GEP requires DENN and non-DENN elements for activation and targeting of Rab27a.

The adaptor protein melanophilin regulates dynamic myosin- Va: cargo interaction and dendrite development in melanocytes (2019)
Journal Article
Robinson, C. L., Evans, R. D., Sivarasa, K., Ramalho, J. S., Briggs, D. A., & Hume, A. N. (2019). The adaptor protein melanophilin regulates dynamic myosin- Va: cargo interaction and dendrite development in melanocytes. Molecular Biology of the Cell, 30(6), 731-809. https://doi.org/10.1091/mbc.E18-04-0237

Regulation of organelle transport by the cytoskeleton is fundamental for eukaryotic survival. Cytoskeleton motors are typically modular proteins with conserved motor and diverse cargo binding domains. Motor:cargo interactions are often indirect and m... Read More about The adaptor protein melanophilin regulates dynamic myosin- Va: cargo interaction and dendrite development in melanocytes.

Residues contributing to drug transport by ABCG2 are localised to multiple drug-binding pockets (2018)
Journal Article
Cox, M. H., Kapoor, P., Briggs, D. A., & Kerr, I. D. (2018). Residues contributing to drug transport by ABCG2 are localised to multiple drug-binding pockets. Biochemical Journal, 475(9), https://doi.org/10.1042/BCJ20170923

Multidrug binding and transport by the ATP binding cassette transporter ABCG2 is a factor in the clinical resistance to chemotherapy in leukaemia, and a contributory factor to the pharmacokinetic profiles of many other prescribed drugs. Despite its i... Read More about Residues contributing to drug transport by ABCG2 are localised to multiple drug-binding pockets.

Inefficient recruitment of kinesin-1 to melanosomes precludes it from facilitating their transport (2017)
Journal Article
Robinson, C. L., Evans, R. D., Briggs, D. A., Ramalho, J. S., & Hume, A. N. (in press). Inefficient recruitment of kinesin-1 to melanosomes precludes it from facilitating their transport. Journal of Cell Science, 130(12), https://doi.org/10.1242/jcs.186064

Microtubules and F-actin, and associated motor proteins, are considered to play complementary roles in long- and short-range organelle transport. However, there is growing appreciation that myosin/F-actin networks can drive long-range transport. In m... Read More about Inefficient recruitment of kinesin-1 to melanosomes precludes it from facilitating their transport.

Identification of residues in ABCG2 affecting protein trafficking and drug transport, using co-evolutionary analysis of ABCG sequences (2015)
Journal Article
Kerr, I., Haider, A. J., Cox, M. H., Jones, N., Goode, A. J., Bridge, K. S., Wong, K., & Briggs, D. (2015). Identification of residues in ABCG2 affecting protein trafficking and drug transport, using co-evolutionary analysis of ABCG sequences. Bioscience Reports, 35(4), Article e00241. https://doi.org/10.1042/BSR20150150

ABCG2 is an ABC (ATP-binding cassette) transporter with a physiological role in urate transport in the kidney and is also implicated in multi-drug efflux from a number of organs in the body. The trafficking of the protein and the mechanism by which i... Read More about Identification of residues in ABCG2 affecting protein trafficking and drug transport, using co-evolutionary analysis of ABCG sequences.

Myosin-Va and dynamic actin oppose microtubules to drive long-range organelle transport (2014)
Journal Article
Evans, R. D., Robinson, C., Briggs, D. A., Tooth, D. J., Ramalho, J. S., Cantero, M., Montoliu, L., Patel, S., Sviderskaya, E. V., & Hume, A. N. (2014). Myosin-Va and dynamic actin oppose microtubules to drive long-range organelle transport. Current Biology, 24(15), 1743-1750. https://doi.org/10.1016/j.cub.2014.06.019

In animal cells, microtubule and actin tracks and their associated motors (dynein, kinesin, and myosin) are thought to regulate long- and short-range transport, respectively [1-8]. Consistent with this, microtubules extend from the perinuclear centro... Read More about Myosin-Va and dynamic actin oppose microtubules to drive long-range organelle transport.

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