Characterization of physiochemical properties of caveolin-1 from normal and prion-infected human brains

// Xiangzhu Xiao 1,* , Pingping Shen 1,2,* , Zerui Wang 1,2,* , Johnny Dang 1 , Alise Adornato 1 , Lewis S. Zou 1 , Zhiqian Dong 1 , Jue Yuan 1 , Jiachun Feng 2 , Li Cui 2 and Wen-Quan Zou 1,2,3 1 Department of Pathology, Case Western Reserve University, Cleveland, OH, USA 2 Institute of Neuroscience Center and Neurology Department, The First Hospital of Jilin University, Changchun, Jilin, China 3 State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China * These authors have Contributed equally to this study Correspondence to: Li Cui, email: // Wen-Quan Zou, email: // Keywords : caveolin-1, human brain, prion disease, solubility, aggregation, Gerotarget Received : June 02, 2017 Accepted : July 12, 2017 Published : July 21, 2017 Abstract Caveolin-1 is a major component protein of the caveolae—a type of flask shaped, 50-100 nm, nonclathrin-coated, microdomain present in the plasma membrane of most mammalian cells. Caveolin-1 functions as a scaffolding protein to organize and concentrate signaling molecules within the caveolae, which may be associated with its unique physicochemical properties including oligomerization, acquisition of detergent insolubility, and association with cholesterol. Here we demonstrate that caveolin-1 is detected in all brain areas examined and recovered in both detergent-soluble and -insoluble fractions. Surprisingly, the recovered molecules from the two different fractions share a similar molecular size ranging from 200 to 2,000 kDa, indicated by gel filtration. Furthermore, both soluble and insoluble caveolin-1 molecules generate a proteinase K (PK)-resistant C-terminal core fragment upon the PK-treatment, by removing ~36 amino acids from the N-terminus of the protein. Although it recognizes caveolin-1 from A431 cell lysate, an antibody against the C-terminus of caveolin-1 fails to detect the brain protein by Western blotting, suggesting that the epitope in the brain caveolin-1 is concealed. No significant differences in the physicochemical properties of caveolin-1 between uninfected and prion-infected brains are observed.