Alzheimer Disease; Cell Membrane; Cell Biology; Endocytosis; Neurosciences; Parkinson Disease; Synapses; Lipid Metabolism
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
Specialized Terms: Synapses; Membrane Traffic; Endocytosis; Clathrin; Dynamin; Phosphoinositides; Lipid Metabolism; Lowe Syndrome; Bar Proteins; Neurodegeneration; Membrane Contact Sites
- PI4P/phosphatidylserine countertransport at ORP5 and ORP8-mediated ER-plasma membrane contacts. Chung J, Torta F, Masai K, Lucast L, Czapla H, Tanner LB, Narayanaswamy P, Wenk MR, Nakatsu F, and De Camilli P. PI4P/phosphatidylserine countertransport at ORP5 and ORP8-mediated ER-plasma membrane contacts. 2015. Science. 349: 428.
- Triggered Ca2+ influx is required for extended synaptotagmin 1-induced ER-plasma membrane tethering. Idevall-Hagren O, Lü A, Xie B, De Camilli P. 2015. Triggered Ca2+ influx is required for extended synaptotagmin 1-induced ER-plasma membrane tethering. EMBO. [Epub ahead of print]
- Massive accumulation of luminal protease-deficient axonal lysosomes at Alzheimer's disease amyloid plaques. Gowrishankar S, Yuan P, Wu Y, Schrag M, Paradise S, Grutzendler J, De Camilli P, Ferguson SM. Proc. Natl. Acad. Sci. U S A. 2015. 112: 3699-3708.
- Three dimensional architecture of extended synaptotagmin-mediated endoplasmic reticulum-plasma membrane contact sites. Fernández-Busnadiego R, Saheki Y, and De Camilli P. 2015. Proc. Natl. Acad. Sci. 112: E2004-E2013.
- Epsin deficiency impairs endocytosis by stalling the actin-dependent invagination of endocytic clathrin coated pits. 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. Elife. 3: e03311.
- A role of OCRL in clathrin-coated pit fission and uncoating revealed by studies of Lowe syndrome cells. Nandez R, Balkin DM, Messa M, Paradise S, Czapla H, Hein MY, Mann M, and De Camilli P. 2014. Elife. 3:e02975.
- Coupling between endocytosis and sphingosine kinase 1 recruitment. 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. Nat Cell Biol. 16: 652-662.
- Structure of a lipid-bound Extended-Synaptotagmin indicates a role in lipid transfer. Schauder CM, Wu X, Saheki Y, Narayanaswamy P, Torta F, Wenk MR, De Camilli P*, and Reinisch KM*. 2014. Nature. 510: 552-5.
- Structural insights into assembly and regulation of the plasma membrane phosphatidylinositol 4-kinase complex. Wu X, Chi RJ, Baskin JM, Lucast L, Burd CG, De Camilli P, and Reinisch KM. 2014. Dev. Cell. 28: 19-29.
- Dynamin triple knockout cells reveal off target effects of a commonly used dynamin inhibitor. Park R, Shen H, Liu L, Liu X, Ferguson SM, and De Camilli P. 2013. J. Cell Sci. 126: 5305-5312.
- PI(4,5)P(2)-dependent and Ca(2+)-regulated ER-PM interactions mediated by the extended synaptotagmins. Giordano F, Saheki Y, Idevall-Hagren O, Colombo S, Pirruccello M, Milosevic I, Gracheva E, Bagriantsev SN, Borgese N, and De Camilli P. (2013) PI(4,5)P(2)-dependent and Ca(2+)-regulated ER-PM interactions mediated by the extended synaptotagmins.
- Calcium occilations-coupled conversion of actin travelling waves to standing oscillations. Wu M, Wu X, and De Camilli P. 2013. Proc. Natl. Acad. Sci. USA. 4: 1339-1344.
- SnapShot: Membrane Curvature Sensors and Generators Shen H, Pirruccello M and De Camilli P. 2012. Cell. 150: 1300-1300.e2
- PtdIns4P synthesis by PI4KIIIα at the plasma membrane and its impact on plasma membrane identity. 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 by PI4KIIIα at the plasma membrane and its impact on plasma membrane identity.
- Optogenetic control of phosphoinositide metabolism. Idevall-Hagren O, Dickson EJ, Hille B, Toomre DK, and De Camilli P. 2012. Proc. Nat. Acad. Sci. 109: 2316-2323.
- Overlapping role of dynamin isoforms in synaptic vesicle endocytosis. 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. Neuron. 70:.1100-1114.
- Recognition of the F&H motif by the Lowe syndrome protein OCRL. Pirruccello M, Swan LE, Folta-Stogniew E, De Camilli P. 2011. Nat Struct Mol Biol. 18: 789-95.
- Coupling between clathrin-dependent endocytic budding and F-BAR-dependent tubulation in a cell-free system. Wu M, Huang B, Graham M, Raimondi A, Heuser JE, Zhuang X, De Camilli P. 2010. Nat Cell Biol. 12: 902-908.
- A phosphoinositide switch controls the maturation and signaling properties of APPL endosomes. Zoncu R, Perera R, Balkin DM, Toomre D, and De Camilli P. 2009. Cell. 136: 1110-1121.
- Structural basis of membrane invagination by F-Bar domains. Frost A, Roux A, Perera R, Spasov K, Destaing O, Egelman EH, De Camilli P, and Unger VM. 2008. Cell. 132: 807-817.
- Sac2/INPP5F is an inositol 4-phosphatase that functions in the endocytic pathway Nakatsu F, Messa M, Nández R, Czapla H, Zou Y, Strittmatter SM, De Camilli P. 2015. J. Cell Biol. 209: 85-95.