N. Davis
Nicholas G. Davis, Ph.D.
Associate Professor

Department of Pharmacology
Wayne State University School of Medicine
540 E. Canfield, 7322 Scott Hall
Detroit MI 48201

Office: (313) 577-8654
Lab: (313) 577-7807
FAX (313) 577-6739
E-mail: ndavis@med.wayne.edu

RESEARCH INTERESTS:

The Davis Lab studies the enzymology and cell biology of protein palmitoylation, a reversible, post-translational protein modification in which fatty acyl moieties (typically, the saturated 16-carbon palmitate) are attached to selected protein cysteine residues.  Many signaling proteins, including key players in cancer and in synaptic transmission, rely on palmitoylation for tethering to membrane action sites.  Palmitoylation's reversibility distinguishes it from other lipid modifications – the regulated addition and removal of this lipid tether provides a powerful mechanism for dynamically controlling a protein's membrane association.  For example, rapid de- and re-palmitoylation cycles controls the dual distribution of H- and N-Ras to Golgi and plasma membranes.  At the synapse, palmitoyl-regulation of the synaptic scaffolding protein PSD-95 controls neurotransmitter receptor deposition and removal, facilitating the synaptic strengthening and weakening of synaptic plasticity.

Despite its significance, palmitoylation has proved difficult to study and the first details of the mechanisms that regulate its addition and removal have only recently begun to emerge.  Indeed, our entry into this field came with our 2002 discovery of a first example palmitoylation enzyme, this being the yeast Golgi-localized protein Akr1.  This first protein acyl transferase (PAT) pointed to the wider DHHC protein family as a potential family of PAT specificities, a supposition borne out by subsequent years of research in many labs.  Many of the 23 human DHHC PATs have been linked to disease, to cancer and also to a spectrum of neurological disorders, including Huntington's Disease, mental retardation, and schizophrenia, indicating a prominent role for palmitoylation in normal brain function.
Davis Lab research currently moves along two fronts.  We continue to mine the yeast genetic system to uncover more of palmitoylation's underlying cell biology, while work in the mammalian brain explores potential roles for palmitoylation in dynamically controlling synaptic function.

Publications:

  • Roth, A.F., Y. Feng, L. Chen, and N.G. Davis (2002) The yeast DHHC cysteine-rich domain protein Akr1p is a palmitoyl transferase.  J. Cell Biol. 159: 23-28.
  • Roth, A.F., J. Wan, A.O. Bailey, B. Sun, J. Kuchar, W.N. Green, B. Phinney, J.R. Yates, III, and N.G. Davis (2006) Global analysis of protein palmitoylation in yeast. Cell 125: 1003-13.
  • Lam, K.K.Y., M. Davey, B. Sun, A.F. Roth, N.G. Davis, and E. Conibear (2006) Palmitoylation by the DHHC-CRD protein Pfa4 regulates the ER exit of Chs3.  J. Cell Biol. 174: 19-25.
  • J. Wan, A.F. Roth, A.O. Bailey, and N.G. Davis (2007) Palmitoylated proteins – purification and identification.  Nature Protocols 2: 135-142.
  • R. Kang, J. Wan, P. Arstikaitis, H. Takahashi, K. Huang, A.O. Bailey, J.X. Thompson, A.F. Roth, R.C. Drisdel, R. Mastro, W.N. Green, J.R. Yates, III, N.G. Davis, A. El-Husseini (2008) Neuronal palmitoyl-proteomics: Dynamic modulation of palmitoylation at the synapse (submitted).

    • Search PubMed for publications from the Davis Lab