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Whitney Marie Cleghorn

Graduate student, 2006-2012, Pharmacology

Research Description

Whitney was in the lab 2006-2012

Whitney is studying the molecular mechanisms of arrestin interaction with receptors in order to elucidate the conformation of active receptor-bound arrestin. To this end, she is using site-directed mutagenesis and site-directed spin labeling/EPR, which allows distance measurements within arrestin and between selected sites in arrestin and the receptor. This will allow us to understand how the arrestin-receptor complex functions as “signalosome” organizer, where receptor-bound arrestin recruits and activates a variety of signaling proteins, including the components of the trafficking machinery, small G proteins and their regulators, ubiquitin ligase, c-Src and related kinases, etc., and how it facilitates the signaling in MAP kinase cascades. She is also studying the molecular mechanisms of arrestin-dependent localization of signaling proteins to the cytoskeleton in living cells and its functional consequences.

She made un unexpected discovery that arrestins directly participate in cell adhesion and motility (two of her first-author papers on this subject will be submitted soon)

Whitney published eight papers and chapters.

Publications (we publish a lot, so search Medline for an update)

Cleghorn, W.M., Bulus, N., Kook, S., Gurevich, V.V., Zent, R., Gurevich, E. V. Non-visual arrestins regulate the focal adhesion formation via small GTPases RhoA and Rac1 independently of GPCRs. Cell Signal 42, 259-269; doi: 10.1016/j.cellsig.2017.11.003 (2018).

Cleghorn, W.M., Branch, K.M., Kook, S.,  Arnette, C., Bulus, N., Zent, R., Kaverina, I., Gurevich, E.V., Weaver, A.M. Gurevich, V.V. Arrestins regulate cell spreading and motility via focal adhesion dynamics. Mol Biol Cell, 26 (4), 622-635 (2015).

Kook, S., Zhan X., Cleghorn, W.M., Benovic, J.L., Gurevich, V.V., Gurevich, E.V. Caspase-cleaved arrestin-2 and BID cooperatively facilitate cytochrome C release and cell death. Cell Death Differ 21 (1), 172-84 (2014). doi: 10.1038/cdd.2013.143

Kim, M., Vishnivetskiy, S.A., Van Eps, N., Alexander, N.S., Cleghorn, W.M., Zhan, X., Hanson, S.M., Morizumi, T., Ernst, O.P., Meiler*, J., Gurevich*, V.V., Hubbell*, W.L. (*corresponding authors) Conformation of receptor-bound visual arrestin. Proc. Natl. Acad. Sci. USA 109, 18407-18412 (2012).

Cleghorn, W.M., Tsakem, E.L., Song, X., Vishnivetskiy, S.A., Seo, J., Chen, J., Gurevich, E.V., and Gurevich, V.V. Progressive reduction of its expression in rods reveales two pools of arrestin-1 in the outer segment with different roles in photoresponse recovery. PLoS One 6 (7), e22797 (2011)

Kim, M., Hanson, S.M., Vishnivetskiy, S.A., Song, X., Cleghorn, W.M., Hubbell, W.L., Gurevich, V.V. Robust self-association is a common feature of mammalian visual arrestin-1. Biochemistry 50, 2235-2242 (2011)

Hanson, S.M., Cleghorn, W.M. , Francis, D.J., Vishnivetskiy, S.A., Raman, D., Song, X., Nair, K.S., Slepak, V.Z., Klug, C.S., and Gurevich, V.V. Arrestin mobilizes signaling proteins to the cytoskeleton and redirects their activity. J Mol Biol 368 , 375-387 (2007).

Gurevich, V.V., Gurevich, E.V., Cleghorn, W.M. Arrestins as multi-functional signaling adaptors. In: Handbook of experimental Pharmacology, vol. 186. Protein-protein interactions as new drug targets (Klussmann, E., and Scott, J., Eds), pp. 15-37. Springer-Verlag, Berlin (2008).