Animals, Laboratory; Mental Disorders; Nervous System Diseases; Organisms, Genetically Modified
NIDA Neuroproteomics Center
The cytoplasm of eukaryotic cells is compartmentalized by intracellular membranes that are interconnected by membrane traffic. We study mechanisms underlying membrane dynamics, with emphasis on membrane transport reactions involved in neurotransmission. Our goal is to advance the understanding of nervous system function in health and disease, neurodegenerative diseases in particular. We also exploit the special properties of synapses to learn about general principles of membrane biology. Within this field, the interplay between bilayer lipids and peripheral membrane proteins is a major focus of our work. These interactions help regulate membrane budding, membrane fission and membrane progression along the secretory and endocytic pathways. A new interest of the lab concerns the role of lipid exchange between bilayers at membrane contact sites that do not result in membrane fusion. In our work we use a wide range of techniques, including biochemistry, structural biology, cell-free systems, optical and electron microscopy, and mouse genetics
- Chung J, Torta F, Masai K, Lucast L, Czapla H, Tanner LB, Narayanaswamy P, Wenk MR, Nakatsu F, and De Camilli P. 2015. PI4P/phosphatidylserine countertransport at ORP5 and ORP8-mediated ER-plasma membrane contacts. Science. 349: 428-423.
- Fernández-Busnadiego R, Saheki Y, and De Camilli P. 2015. Three dimensional architecture of extended synaptotagmin-mediated endoplasmic reticulum-plasma membrane contact sites. Proc. Natl. Acad. Sci. 112: E2004-E2013.
- Messa M, Fernanez-Busnadiego R, Sun EW, Chen H, Czapla H, Wrasman K, Wu Y, Ko G, Ross T, Wendland B, and De Camilli P. 2014. Epsin deficiency impairs endocytosis by stalling the actin-dependent invagination of endocytic clathrin coated pits. Elife. 3: e03311
- Nandez R, Balkin DM, Messa M, Paradise S, Czapla H, Hein MY, Mann M, and De Camilli P. 2014. A role of OCRL in clathrin-coated pit fission and uncoating revealed by studies of Lowe syndrome cells. Elife. 3:e02975.
- Shen H, Giordano F, Wu Y, Chan J, Zhu C, Milosevic I, Wu X, Yao K, Chen B, Baumgart T, Sieburth D, De Camilli P. 2014. Coupling between endocytosis and sphingosine kinase 1 recruitment. Nat Cell Biol. 16: 652-662
- Schauder CM, Wu X, Saheki Y, Narayanaswamy P, Torta F, Wenk MR, De Camilli P*, and Reinisch KM*. 2014. Structure of a lipid-bound Extended-Synaptotagmin indicates a role in lipid transfer. Nature. 510:552-5.
- Wu X, Chi RJ, Baskin JM, Lucast L, Burd CG, De Camilli P, and Reinisch KM. 2014. Structural insights into assembly and regulation of the plasma membrane phosphatidylinositol 4-kinase complex. Dev. Cell. 28: 19-29.
- Park R, Shen H, Liu L, Liu X, Ferguson SM, and De Camilli P. 2013. Dynamin triple knockout cells reveal off target effects of a commonly used dynamin inhibitor. J. Cell Sci. 126: 5305-5312.
- Giordano F, Saheki Y, Idevall-Hagren O, Colombo S, Pirruccello M, Milosevic I, Gracheva E, Bagriantsev SN, Borgese N, and De Camilli P. PI(4,5)P2-dependent and Ca2+-regulated ER-PM interactions mediated by the extended-synaptotagmins. Cell. 153: 1494-15
- Wu M, Wu X, and De Camilli P. 2013. Calcium occilations-coupled conversion of actin travelling waves to standing oscillations. Proc. Natl. Acad. Sci. USA. 4: 1339-1344.
- Shen H, Pirruccello M and De Camilli P. 2012. SnapShot: Membrane Curvature Sensors and Generators. Cell. 150: 1300-1300.e2
- Nakatsu F, Baskin JM, Chung J, Tanner LB, Shui G, Lee SY, Pirruccello M, Hao M, Ingolia NT, Wenk MR, and De Camilli P. 2012. PtdIns4P synthesis at the plasma membrane and its impact on PtdIns(4,5)P2 dynamics to control plasma membrane identity. J. Cell
- Idevall-Hagren O, Dickson EJ, Hille B, Toomre DK, and De Camilli P. 2012. Optogenetic control of phosphoinositide metabolism. Proc. Nat. Acad. Sci. 109: 2316-2323.
- Raimondi A, Ferguson SM, Lou X, Armbruster M, Paradise S, Giovedi S, Messa M, Kono N, Takasaki J, Cappello V, O'Toole E, Ryan TA and De Camilli P. 2011. Overlapping role of dynamin isoforms in synaptic vesicle endocytosis. Neuron. 70:1100-14.
- Pirruccello M, Swan LE, Folta-Stogniew E, De Camilli P. 2011. Recognition of the F&H motif by the Lowe syndrome protein OCRL. Nat Struct Mol Biol. 18:789-95.
- Wu M, Huang B, Graham M, Raimondi A, Heuser JE, Zhuang X, De Camilli P. 2010. Coupling between clathrin-dependent endocytic budding and F-BAR-dependent tubulation in a cell-free system. Nat Cell Biol. 12:902-908.
- Zoncu R, Perera R, Balkin DM, Toomre D, and De Camilli P. 2009. A phosphoinositide switch controls the maturation and signaling properties of APPL endosomes. Cell. 136: 1110-1121.
- Frost A, Roux A, Perera R, Spasov K, Destaing O, Egelman EH, De Camilli P, and Unger VM. 2008. Structural basis of membrane invagination by F-Bar domains. Cell. 132: 807-817.