Molecular cell biology of cytoskeletal transport
Personal group site
Molecular motors have critical roles in the trafficking of organelles, vesicles and macromolecules within the cytoplasm, and aberrant motor function is associated with diseases such as neurodegeneration. Our goal is to understand how motor complexes recognise different cargoes and deliver them to the right place. We have a long-standing interest in cytoplasmic transport of messenger RNAs, a process widely used to control where specific proteins operate, but have also become intrigued by how motors sort other types of cargo. We use complementary techniques in our studies, including Drosophila genetics, in vivo imaging, biochemistry, structural biology and single molecule imaging of cargo transport in vitro.
The questions we are interested in include:
- How does the microtubule-based motor dynein recognises specific mRNAs, vesicles and organelles and sort them to different destinations?
- How is the action of multiple motors bound to a single cargo orchestrated?
- How is transport regulated by extrinsic cues, and how do these events contribute to polarised cell functions?
- How does disruption of motor function contribute to neurological diseases, and can these defects be reversed?
- Fumagalli, L.*, Young, FL.*, Boeynaems, S.*, De Decker, M., Mehta, AR., Swijsen, A., Fazal, R., Guo, W., Moisse, M., Beckers, J., Dedeene, L., Selvaraj, BT., Vandoorne, T., Madan, V., van Blitterswijk, M., Raitcheva, D., McCampbell, A., Poesen, K., Gitler, AD., Koch, P., Vanden Berghe, P., Thal, DR., Verfaillie, C., Chandran, S., Van Den Bosch, L., Bullock, SL.**, Van Damme, P**. *Joint first authors **Joint corresponding authors (2021)
C9orf72-derived arginine-containing dipeptide repeats associate with axonal transport machinery and impede microtubule-based motility.
Science Advances 7: no. 15, eabg3013 DOI: 10.1126/sciadv.abg3013
- McClintock M.A., Dix C.I., Johnson C.M., McLaughlin S.H., Maizels R.J., Hoang, H.-T. and Bullock S.L. (2018)
RNA-directed activation of cytoplasmic dynein-1 in reconstituted transport RNPs.
eLife 7: doi: 10.7554/eLife.36312.
- Vagnoni A. and Bullock SL (2018)
A cAMP/PKA/kinesin-1 axis promotes axonal transport of mitochondria in ageing Drosophila neurons.
Curr Biol 28: 1265-1272 (SB and AV are corresponding authors)
- Baumbach J., Murthy A., McClintock M.A., Dix, C.I., Zalyte, R., Hoang, HT., Bullock, SL. (2017)
Lissencephaly-1 is a context-dependent regulator of the human dynein complex.
Elife 6: doi: 10.7554/eLife.21768
- Mofatteh M. and Bullock S.L. (2017)
SnapShot: Subcellular mRNA localization.
Cell 169: 178-178
- Hoang H.T., Schlager M.A., Carter A.P. and Bullock S.L. (2017)
DYNC1H1 mutations associated with neurological diseases compromise processivity of dynein-dynactin-cargo adaptor complexes.
PNAS 114: E1597-E1606.
- Lucas Albacete Albacete
- Yaiza Andrés Jeske
- Sabila Chilaeva
- Li Jin
- Razina Kazi
- Mark McClintock
- Sankar Meenakshi Sundaram