DATASET BRIEF Analysis of membrane microdomain-associated proteins in the insular cortex of post-mortem human brain Áine T. Behan 1 , Martina Foy 2 , Kieran Wynne 3 , Michael Clarke 3 , Matthew Sullivan 2 , David R. Cotter 1 and Patricia B. Maguire 2 1 Department of Psychiatry, Royal College of Surgeons in Ireland, RCSI Education and Research Centre, Beaumont Hospital, Dublin, Ireland 2 School of Medicine and Medical Science, Conway Institute for Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Ireland 3 School of Biomolecular and Biomedical Science, Conway Institute for Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Ireland Membrane microdomains (MM) are membrane rafts within the cell membrane enriched in cholesterol and glycosphingolipids that have been implicated in the trafficking and sorting of membrane proteins, secretory and endocytotic pathways, and signal transduction. To date, MM have not been characterised in the human brain. We reason that by identifying MM in the nor- mal human cortex, we may better understand the molecular mechanisms of human brain dys- function. To characterize the protein composition of MM in the human brain, we have carried out a comprehensive proteomic analysis of detergent resistant membranes (DRMs) associated proteins derived from human postmortem insular cortex using 1-DE separation prior to LC coupled to MS/MSor GeLC-MS/MS. Eighty five proteins were identified including 57 unique to human brain cortex DRMs (by comparison with DRM proteins reported in other cell types). High levels of signal transduction, cell adhesion, cell transport and cell trafficking proteins were identified including synaptic proteins such as synapsin II and synaptic vesicle membrane pro- tein, mitochondrial proteins such as ATPase subunits and metabolic enzymes such as malate dehydrogenase. This data will facilitate our understanding of protein expression changes within membranes in candidate brain regions in human brain diseases such as schizophrenia, bipolar disorder and other psychiatric and neurodegenerative disorders. Received: January 17, 2007 Revised: May 2, 2007 Accepted: May 30, 2007 Keywords: Detergent-resistant membranes / Membrane microdomains 1324 Proteomics Clin. Appl. 2007, 1, 1324–1331 Membrane microdomains (MM) are defined by their cholesterol and sphingolipid-rich nature, cytoskeletal associ- ation and resistance to detergent extraction. Numerous roles haven been ascribed to MMs in particular their involvement as vehicles of endocytosis and trafficking during signaling [1]. Studies analysing protein changes potentially contribut- ing to human brain diseases have identified numerous MM associated proteins as candidate players [2–4]. This is espe- cially relevant in human brain disease where MMs are thought to modulate neurotransmitter receptor activation, neurotransmitter receptor uptake and the aggregation of signalling components [1]. Characterising the composition of brain MM associated proteins will provide a platform to understanding the role of MM and their resident proteins in human brain disease. To date, several proteomic studies on the entire brain, its compartments, and organelles have been described in ani- mal models [5, 6] as well as protein profiles of individual Correspondence: Dr. Áine T. Behan, Dept of Psychiatry, RCSI ERC, Smurfit Building, Beaumont Hospital, Dublin 9, Ireland E-mail: abehan@rcsi.ie Fax: 1353-1-809-3098 Abbreviations: DRM, detergent-resistant membrane; MM, mem- brane microdomain; PIC, protease inhibitor cocktail DOI 10.1002/prca.200700047  2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.clinical.proteomics-journal.com