Penultimate author

Mature proteins can be modified in several ways: the attachment of fats, for example, can facilitate their binding to cell membranes. Unusually, palmitoylation — attachment of the fat palmitic acid — is reversible, and so may regulate protein–membrane interactions. Last year, neuroscientist Alaa El-Husseini of the University of British Columbia in Canada teamed up with a group led by Nicholas Davis at Wayne State University in Detroit, Michigan, to use proteomics to explore the role of palmitoylation in the brain. They found significant involvement of this modification at synapses — junctions between nerves by which they signal to one another. Just a couple of days after submitting the paper on page 904, El-Husseini unexpectedly passed away. Davis discusses challenges the team faced.

What events led up to this work?

In 2002, Alaa showed that the firing of nerve impulses by synapses regulates the palmitoylation of a key synaptic protein called PSD-95. Palmitoylation has been remarkably understudied. My group developed a method for identifying palmitoylated proteins in yeast and Alaa was eager to apply it to the brain.

Were you pleased with the findings?

We were a bit overwhelmed to discover several hundred palmitoylated proteins participating in diverse areas of neuronal function, particularly at the synapse. Even more surprising was finding that the palmitoylation of the protein Cdc42 played a critical role in the formation of dendritic spines — tiny protrusions on neurons that change in number and shape in response to neuronal activity. Alaa was thrilled because he had long believed palmitoylation to be an important regulator of synapse function.

How did Dr El-Husseini's death affect publication?

We were all deeply saddened by Alaa's death. It also affected us on a professional level. When the reviewers asked for experiments to extend one of our findings, Alaa's students and postdocs really pulled together, driven by the prospect of having a Nature publication as tribute to him. They designed and performed a difficult series of experiments, which added a huge amount to the paper.

Where will you go from here?

I've worked with yeast for 20 years, but I am enjoying the foray into neuroscience. I'm intrigued by links that have been made between palmitoylation enzymes and various neurological diseases, including Huntington's disease and schizophrenia. We would like to apply quantitative proteomics to learn how changes in palmitoylation might participate in these diseases.