I have developed, in collaboration with the Kuhlman lab at UNC, a novel optogenetic tool. This tool affords me the ability to spatially and temporally recruit proteins of interest to the microtubule plus end, allowing me to determine the spatial and temporal importance of these proteins throughout the cell cycle. I have used this tool to investigate the role of temporal cross linking of the actin and microtubule networks. I am optimistic that the optogenetic tool that I developed can be transitioned into the organism, providing a means to investigate the spatial and temporal role of microtubule associated proteins during different stages of development at the sub cellular level within a developing animal.
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Publication:
Adikes, R.C., Hallett, R.A., Saway, B.F., Kuhlman, B., Slep, K.C. (2018) Control of cytoskeletal dynamics via light mediated microtubule actin crosslinking. JCB 217(2) 779-793. DOI: 10.1083/jcb.201705190 Prepint on BioRxiv DOI: https://doi.org/10.1101/142414 |
Publication:
Haase, K.P.*, Fox, J.C.*, Brynes, A.E.*, Adikes, R.C.*, Speed, S.K., Haase, J., Friedman, B., Cook, D.M., Bloom, K., Rusan, N.M., Slep, K.C. (2017) The S.cerevisiae XMAP215 family member Stu2 arranges its TOG domain array using a structurally distinct 15nm parallel coiled coil. *These authors contributed equally. Molecular Biology of the Cell. |
Microtubules (MTs) are cytoskeletal polymers responsible for multiple cytoplasmic activities: enabling intracellular transport, stabilizing the cell’s shape, and forming the mitotic spindle to separate chromosomes during mitosis. MT-associated proteins (MAPs) localize to MTs where they modulate MT dynamics through molecular and structural changes to the MTs. Members of a subgroup of MAPs that specifically localize to the MT plus end are referred to as +TIPs. A group of highly conserved +TIPs, known as the XMAP215 family, accelerate MT assembly and promote MT growth. XMAP215 family members promote polymerization via TOG (tumor over expressed gene) domains that bind to tubulin heterodimers. Studies of XMAP215 family members in multiple species (S. pombe, C. elegans, Xenopus egg extracts, Drosophila and HeLa cells) have shown that they play an essential role during interphase and mitosis, as their depletion leads to decreased MT growth rates and short spindles or defects in spindle architecture. Members of the XMAP215 family contain a varying number of N-terminal TOG domains, however, the structure and functional role of the C-terminal region remains unknown. My work in collaboration with three UNC undergraduate has shed light on the role of this C-terminal domain. |