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Pietro De Camilli, M.D. - "Lipid Signaling in the Control of Membrane Dynamics and Interactions"

(Departments of Neuroscience and Cell Biology, Howard Hughes Medical Institute, Kavli Institute for Neuroscience, Yale University School of Medicine)
When Sep 09, 2016
from 03:00 PM to 04:00 PM
Where Tigem Auditorium "Vesuvius"
Contact Name
Contact Phone 081-19230659
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Curriculum Vitae

Contribution to Science (selected papers since the mid-1990’)

1.  Molecular mechanisms in endocytosis
I have made numerous contributions to the elucidation of sequence of events and regulatory mechanisms involved in endocytosis at the neuronal synapse and in other systems. I have also identified and functionally characterized general and synapse-specific factors implicated in endocytosis.

McPherson PS, Garcia EP, Slepnev V, David C, Zhang X, Grabs D, Sossin WS, Bauerfeind R, Nemoto Y, and De Camilli P.  1996.  A presynaptic inositol-5-phosphatase.  Nature.  379: 353-357.

Takei K, Haucke V, Slepnev V, Farsad K, Salazar M, Chen H, and De Camilli P.  1998.  Generation of coated intermediates of clathrin-mediated endocytosis on protein-free liposomes.  Cell.  94: 131-141.

Milosevic I, Giovedi S, Lou X, Raimondi A, Collesi C, Paradise S, Shen H, O’Toole E, Ferguson S, Cremona O, and De Camilli P.  2011.  Recruitment of endophilin to clathrin coated pit necks is required for uncoating but is dispensable for fission.  Neuron.  72: 587-601.  PMCID: PMC3258500.

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.  PMCID: PMC4161027.

2.  The fission reaction of endocytosis
I provided key insight into the mechanism of action of the GTPase dynamin in the fission reaction of endocytosis, including endocytosis at neuronal synapses.

Takei K, McPherson P, Schmid SL, and De Camilli P.  1995.  Tubular membrane invaginations coated in dynamin rings are induced by GTP-gs in nerve terminals.  Nature.  374: 186-190.

Roux A, Uyhazi K, Frost A, and De Camilli P.  2006.  GTP-dependent twisting of dynamin implicates both constriction and tension in membrane fission.  Nature.  441: 528-531.

Ferguson SM, Brasnjo G, Hayashi M, Wölfel M, Collesi C, Giovedi S, Raimondi A, Gong LW, Paradise S, O’Toole E, Flavell R, Cremona O, Miesenböck, Ryan TA, and De Camilli P.  2007. A selective activity-dependent requirement for dynamin 1 in synaptic vesicle endocytosis.  Science.  316: 570-574.

Ferguson S, Raimondi A, Paradise S, Shen H, Mesaki K, Destaing O, Ko G, Cremona O, O'Toole E, and De Camilli P.  2009. Coordinated actions of actin and BAR proteins upstream of dynamin at endocytic clathrin-coated pits.  Dev. Cell.  17: 811-822.  PMCID: PMC2861561.

3.  Bilayer deforming proteins and membrane shape
As part of my studies of endocytosis at the neuronal synapse, I established that some endocytic proteins bind directly to membrane bilayers and also deform them, thus helping coordinate the assembly of endocytic factors with membrane deformation. This work, which demonstrated for the first time the membrane shaping properties of BAR domain containing proteins, had a seminal impact in cell biology and started a completely new field of research.

Takei K, Slepnev VI, Haucke V, and De Camilli P.  1999.  Functional partnership between amphiphysin and dynamin in clathrin-mediated endocytosis.  Nat. Cell Biol.  1: 33-39.

Farsad K, Ringstad N, Takei K, Floyd SR, and De Camilli P.  Generation of high curvature membranes mediated by direct endophilin-bilayer interactions.  2001.  J. Cell Biol.  155: 193-200.

Itoh T, Erdmann KS, Roux A, Habermann B, Werner H, and De Camilli P.  2005.  Dynamin and the actin cytoskeleton cooperatively regulate plasma membrane invagination by BAR and F-BAR proteins.  Dev. Cell.  6: 791-804.

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.  PMCID: PMC2384079.

4.  Phosphoinositide metabolism in membrane traffic
I discovered the role of phosphoinositide metabolism in synaptic vesicle recycling at synapses.  Building on this finding, I made several additional key contributions to the field of phosphoinositide signaling (basic mechanisms, role in disease, methodology to study phosphoinositide metabolism, including optogenetic approaches).

Cremona O, Di Paolo G, Wenk M, Luthi A, Kim WT, Takei K, Daniell L, Nemoto Y, Flavell RA, McCormick DA and De Camilli P.  1999.  Essential role of phosphoinositide metabolism in synaptic vesicle recycling.  Cell.  99: 179-188.

Di Paolo G, and De Camilli P.  2006.  Phosphoinositides in cell regulation and membrane dynamics.  Nature.  443: 651-657 (cited more than 1500 times).

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.  PMCID: PMC2705806.

Baskin JM, Wu X, Christiano R, Oh M, Schauder CM, Gazzerro E, Messa M, Baldassari S, Assereto S, Biancheri R, Zara F, Minetti C, Raimondi A, Simons M, Walther TC, Reinisch KM, and De Camilli P.  2015.  The leukodystrophy protein FAM126A/Hyccin regulates PI4P synthesis at the plasma membrane.  Nat. Cell Biol.  18: 132-138.  PMCID: PMC4689616

5.  Lipid dynamics at membrane contact sites
I revealed new mechanisms in the cross-talk between the ER and other membranes mediated by direct contact sites. I also provided evidence for a role of these contacts in lipid transfer.

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)P2-dependent and Ca2+-regulated ER-PM interactions mediated by the extended-synaptotagmins. Cell.  153: 1494-1509.  PMCID: PMC3716012.

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: 552-555.  PMCID: PMC4135724

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: 428-432. (News and Views in Nature: Menon and Levine, Nature 525, 191-192, 2015).  PMCID: PMC4638224

Dong R, Saheki Y, Swarup S, Lucast L, Harper JW, De Camilli P.  2016.  Endosome-ER contacts control actin nucleation and retromer function through VAP-dependent regulation of PI4P.  Cell.  166: 408-423.  PMCID: PMC4963242

Complete List of Published Work in My Bibliography:

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