Cells require ordered movement of proteins and lipids from one membrane-bound compartment to another, while maintaining the organization, function and heterogeneity of the donor and acceptor membranes;vesicular membrane traffic carries out these functions. Clathrin coated vesicles are the most prominent form of traffic from the plasma membrane to endosomes (endocytosis), a pathway by which various ligands and their receptors enter cells. Clathrin coated vesicles are also important for traffic between endosomes and the trans-Golgi network (TGN). We propose to continue our studies of molecular mechanisms in clathrin-mediated membrane traffic, using direct observation by live-cell imaging with single-molecular sensitivity and high spatial and temporal resolution, to answer the following questions. (1) What are the molecular events required to initiate formation of a clathrin coated pit? (2) What are the molecular components of coats trapped at various stages of growth and closure: early and late abortive coated pits, and pits stalled at a relatively late stage, by imposing tension of the membrane and by inhibiting actin dynamics? (3) What is the mechanism of clathrin uncoating mediated by Hsc70 and its co-chaperone auxilin and how is the uncoating coordinated with assembly so that the two processes do not compete?
Vesicular membrane traffic is the principal mechanism for moving proteins and lipids among membrane-bound compartments in a cell. Clathrin coated vesicles are the most prominent form of traffic from the plasma membrane to endosomes (endocytosis), a pathway by which ligands such as hormones, transferrin, immunoglobulins, LDL, viruses and their receptors enter cells.
|Böcking, Till; Aguet, François; Rapoport, Iris et al. (2014) Key interactions for clathrin coat stability. Structure 22:819-29|
|Cocucci, Emanuele; Gaudin, Raphaël; Kirchhausen, Tom (2014) Dynamin recruitment and membrane scission at the neck of a clathrin-coated pit. Mol Biol Cell 25:3595-609|
|Hagemann, Anja I H; Kurz, Jennifer; Kauffeld, Silke et al. (2014) In vivo analysis of formation and endocytosis of the Wnt/?-catenin signaling complex in zebrafish embryos. J Cell Sci 127:3970-82|
|Lu, Lei; Hannoush, Rami N; Goess, Brian C et al. (2013) The small molecule dispergo tubulates the endoplasmic reticulum and inhibits export. Mol Biol Cell 24:1020-9|
|Martin, Robert M; Rino, Jose; Carvalho, Celia et al. (2013) Live-cell visualization of pre-mRNA splicing with single-molecule sensitivity. Cell Rep 4:1144-55|
|Boulant, Steeve; Stanifer, Megan; Kural, Comert et al. (2013) Similar uptake but different trafficking and escape routes of reovirus virions and infectious subvirion particles imaged in polarized Madin-Darby canine kidney cells. Mol Biol Cell 24:1196-207|
|Martinelli, Roberta; Kamei, Masataka; Sage, Peter T et al. (2013) Release of cellular tension signals self-restorative ventral lamellipodia to heal barrier micro-wounds. J Cell Biol 201:449-65|
|Tacheva-Grigorova, Silvia K; Santos, Antonio J M; Boucrot, Emmanuel et al. (2013) Clathrin-mediated endocytosis persists during unperturbed mitosis. Cell Rep 4:659-68|
|Strang, Blair L; Boulant, Steeve; Chang, Lynne et al. (2012) Human cytomegalovirus UL44 concentrates at the periphery of replication compartments, the site of viral DNA synthesis. J Virol 86:2089-95|
|Kural, Comert; Kirchhausen, Tom (2012) Live-cell imaging of clathrin coats. Methods Enzymol 505:59-80|
Showing the most recent 10 out of 38 publications