Podle hesla „exocyst“ vše od historie až po 31. 12. 2006
Guo W, Tamanoi F, Novick P.
Nat Cell Biol. 2001 Apr;3(4):353-60.
Spatial regulation of the exocyst complex by Rho1 GTPase.
Terbush DR, Guo W, Dunkelbarger S, Novick P.
Methods Enzymol. 2001;329:100-10.
Purification and characterization of yeast exocyst complex.
Sugihara K, Asano S, Tanaka K, Iwamatsu A, Okawa K, Ohta Y.
Nat Cell Biol. 2002 Jan;4(1):73-8.
The exocyst complex binds the small GTPase RalA to mediate filopodia formation.
Moskalenko S, Henry DO, Rosse C, Mirey G, Camonis JH, White MA.
Nat Cell Biol. 2002 Jan;4(1):66-72.
The exocyst is a Ral effector complex.
Ponnambalam S, Baldwin SA.
Mol Membr Biol. 2003 Apr-Jun;20(2):129-39.
Constitutive protein secretion from the trans-Golgi network to the plasma membrane.
Wang S, Hsu SC.
Hybrid Hybridomics. 2003 Jun;22(3):159-64.
Immunological characterization of exocyst complex subunits in cell differentiation.
Dobbelaere J, Barral Y.
Science. 2004 Jul 16;305(5682):393-6.
Spatial coordination of cytokinetic events by compartmentalization of the cell cortex.
Guo W, Novick P.
Trends Cell Biol. 2004 Feb;14(2):61-3.
The exocyst meets the translocon: a regulatory circuit for secretion and protein synthesis?
Wu S, Mehta SQ, Pichaud F, Bellen HJ, Quiocho FA.
Nat Struct Mol Biol. 2005 Oct;12(10):879-85. Epub 2005 Sep 11.
Sec15 interacts with Rab11 via a novel domain and affects Rab11 localization in vivo.
Langevin J, Morgan MJ, Sibarita JB, Aresta S, Murthy M, Schwarz T, Camonis J, Bellaiche Y.
Dev Cell. 2005 Sep;9(3):355-76.
Drosophila exocyst components Sec5, Sec6, and Sec15 regulate DE-Cadherin trafficking from
recycling endosomes to the plasma membrane.
Stuart LM, Boulais J, Charriere GM, Hennessy EJ, Brunet S, Jutras I, Goyette G, Rondeau C, Letarte
S, Huang H, Ye P, Morales F, Kocks C, Bader JS, Desjardins M, Ezekowitz RA.
Nature. 2006 Dec 6; [Epub ahead of print]
A systems biology analysis of the Drosophila phagosome.
Wang S, Hsu SC.
Biochem Soc Trans. 2006 Nov;34(Pt 5):687-90.
The molecular mechanisms of the mammalian exocyst complex in exocytosis.
Novick P, Medkova M, Dong G, Hutagalung A, Reinisch K, Grosshans B.
Biochem Soc Trans. 2006 Nov;34(Pt 5):683-6.
Interactions between Rabs, tethers, SNAREs and their regulators in exocytosis.
Zhang G, Kashimshetty R, Ng KE, Tan HB, Yeong FM.
J Cell Biol. 2006 Jul 17;174(2):207-20.
Exit from mitosis triggers Chs2p transport from the endoplasmic reticulum to mother-daughter
neck via the secretory pathway in budding yeast.
Munson M, Novick P.
Nat Struct Mol Biol. 2006 Jul;13(7):577-81.
The exocyst defrocked, a framework of rods revealed.
van Dam EM, Robinson PJ.
Int J Biochem Cell Biol. 2006;38(11):1841-7. Epub 2006 May 9.
Ral: mediator of membrane trafficking.
Sivaram MV, Furgason ML, Brewer DN, Munson M.
Nat Struct Mol Biol. 2006 Jun;13(6):555-6. Epub 2006 May 14.
The structure of the exocyst subunit Sec6p defines a conserved architecture with diverse
roles.
Gerges NZ, Backos DS, Rupasinghe CN, Spaller MR, Esteban JA.
EMBO J. 2006 Apr 19;25(8):1623-34. Epub 2006 Apr 6.
Dual role of the exocyst in AMPA receptor targeting and insertion into the postsynaptic
membrane.
1: Nat Cell Biol. 2002 Jan;4(1):73-8.
The exocyst complex binds the small GTPase RalA to mediate filopodia formation.
Sugihara K, Asano S, Tanaka K, Iwamatsu A, Okawa K, Ohta Y.
Hematology Division, Department of Medicine, Brigham and women's Hospital,
Harvard Medical School, Boston, Massachusetts 02115, USA.
The Ras-related small GTPase RalA is involved in controlling actin cytoskeletal remodelling and
vesicle transport in mammalian cells. We identified the mammalian homologue of Sec5, a subunit of
the exocyst complex determining yeast cell polarity, as a specific binding partner for GTP-ligated RalA.
Inhibition of RalA binding to Sec5 prevents filopod production by tumor necrosis factor-alpha (TNFalpha) and interleukin-1 (IL-1) and by activated forms of RalA and Cdc42, signalling intermediates
downstream of these inflammatory cytokines. We propose that the RalA-exocyst complex interaction
integrates the secretory and cytoskeletal pathways.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
PMID: 11744922 [PubMed - indexed for MEDLINE]
2: Nat Cell Biol. 2002 Jan;4(1):66-72.
The exocyst is a Ral effector complex.
Moskalenko S, Henry DO, Rosse C, Mirey G, Camonis JH, White MA.
Department of Cell Biology, University of Texas Southwestern Medical Center,
5323 Harry Hines Blvd, Dallas, Texas 75235-9039, USA.
Delivery of cytoplasmic vesicles to discrete plasma-membrane domains is critical for establishing and
maintaining cell polarity, neurite differentiation and regulated exocytosis. The exocyst is a multisubunit
complex required for vectorial targeting of a subset of secretory vesicles. Mechanisms that regulate
the activity of this complex in mammals are unknown. Here we show that Sec5, an integral component
of the exocyst, is a direct target for activated Ral GTPases. Ral GTPases regulate targeting of
basolateral proteins in epithelial cells, secretagogue-dependent exocytosis in neuroendocrine cells
and assembly of exocyst complexes. These observations define Ral GTPases as critical regulators of
vesicle trafficking.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
PMID: 11740492 [PubMed - indexed for MEDLINE]
3: Nat Cell Biol. 2001 Apr;3(4):353-60.
Spatial regulation of the exocyst complex by Rho1 GTPase.
Guo W, Tamanoi F, Novick P.
Department of Cell Biology, Yale University School of Medicine, New Haven,
Connecticut 06520-8002, USA.
Spatial regulation of membrane traffic is fundamental to many biological processes, including epithelial
cell polarization and neuronal synaptogenesis. The multiprotein exocyst complex is localized to sites of
polarized exocytosis, and is required for vesicle targeting and docking at specific domains of the
plasma membrane. One component of the complex, Sec3, is thought to be a spatial landmark for
polarized exocytosis. We have searched for proteins that regulate the polarized localization of the
exocyst in the budding yeast Saccharomyces cerevisiae. Here we report that certain rho1 mutant
alleles specifically affect the localization of the exocyst proteins. Sec3 interacts directly with Rho1 in its
GTP-bound form, and functional Rho1 is needed both to establish and to maintain the polarized
localization of Sec3. Sec3 is not the only mediator of the effect of Rho1 on the exocyst, because some
members of the complex are correctly targeted independently of the interaction between Rho1 and
Sec3. These results reveal the action of parallel pathways for the polarized localization of the exocytic
machinery, both of which are under the control of Rho1, a master regulator of cell polarity.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
PMID: 11283608 [PubMed - indexed for MEDLINE]
4: Methods Enzymol. 2001;329:100-10.
Purification and characterization of yeast exocyst complex.
Terbush DR, Guo W, Dunkelbarger S, Novick P.
Department of Biochemistry and Molecular Biology, Uniformed Services University
of the Health Sciences, Bethesda, Maryland 20814, USA.
Publication Types:
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
PMID: 11210526 [PubMed - indexed for MEDLINE]
5: Mol Membr Biol. 2003 Apr-Jun;20(2):129-39.
Constitutive protein secretion from the trans-Golgi network to the plasma membrane.
Ponnambalam S, Baldwin SA.
School of Biochemistry and Molecular Biology, University of Leeds, UK.
s.ponnambalam@bmb.leeds.ac.uk
Constitutive secretion is used to deliver newly synthesized proteins to the cell surface and to the
extracellular milieu. The trans-Golgi network is a key station along this route that mediates sorting of
proteins into distinct transport pathways, aided in part by clathrin and adaptor proteins. Subsequent
movement of proteins to the plasma membrane can occur either directly or via the endocytic pathway.
Moreover, multiple, parallel pathways from the trans-Golgi network to the plasma membrane appear to
exist, not only in complex, polarized cells such as epithelial cells and neurons, but also in relatively
simple cells such as fibroblasts. In addition to typical secretory vesicles, these pathways involve both
small, pleiomorphic transport containers and relatively large tubular-saccular carriers that travel along
cytoskeletal tracks. While production and movement of these membranous structures are typically
described as constitutive, recent studies have revealed that these key steps in secretion are tightly
regulated by Ras-superfamily GTPases, members of the protein kinase D family and tethering
complexes such as the exocyst.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 12851070 [PubMed - indexed for MEDLINE]
6: Hybrid Hybridomics. 2003 Jun;22(3):159-64.
Immunological characterization of exocyst complex subunits in cell
differentiation.
Wang S, Hsu SC.
Department of Cell Biology and Neurosciences, Rutgers University, Piscataway, NJ
08854, USA.
We have generated monoclonal antibodies (MAbs) against three proteins sec6, sec15, and exo84.
These proteins have been shown to be components of the exocyst complex, a macromolecule
required for many biological processes such as kidney epithelial formation and neuronal development.
These antibodies can detect the three proteins by enzyme-linked immunoadsorbent assay (ELISA),
Western blotting, immunofluorescence microscopy, and immunoprecipitation. Using these antibodies,
we found that the three proteins have similar subcellular localization which changes upon cell
differentiation. These three proteins also co-immunoprecipitate with each other. These results suggest
that at least three exocyst subunits associate with each other in vivo and redistribute in response to
cell differentiation. In the future, these antibodies should be useful in the cell biological and functional
analysis of the exocyst complex under physiological and pathological conditions.
Publication Types:
Research Support, U.S. Gov't, P.H.S.
PMID: 12954101 [PubMed - indexed for MEDLINE]
1: Science. 2004 Jul 16;305(5682):393-6.
Spatial coordination of cytokinetic events by compartmentalization of the cell cortex.
Dobbelaere J, Barral Y.
Institute of Biochemistry, Swiss Federal Institute of Technology, ETH-Honggerberg, 8093 Zurich,
Switzerland.
During cytokinesis, furrow ingression and plasma membrane fission irreversibly separate daughter
cells. How actomyosin ring assembly and contraction, vesicle fusion, and abscission are spatially
coordinated was unknown. We found that during cytokinesis septin rings, located on both sides of the
actomyosin ring, acted as barriers to compartmentalize the cortex around the cleavage site.
Compartmentalization maintained diffusible cortical factors, such as the exocyst and the polarizome, to
the site of cleavage. In turn, such factors were required for actomyosin ring function and membrane
abscission. Thus, a specialized cortical compartment ensures the spatial coordination of cytokinetic
events.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 15256669 [PubMed - indexed for MEDLINE]
2: Trends Cell Biol. 2004 Feb;14(2):61-3.
The exocyst meets the translocon: a regulatory circuit for secretion and protein synthesis?
Guo W, Novick P.
Department of Biology, University of Pennsylvania, 405 S. University Avenue, Philadelphia, PA 19014,
USA. guowei@sas.upenn.edu
The translocon is responsible for the translocation of proteins across the membrane of the
endoplasmic reticulum into its lumen, whereas the exocyst acts at the other end of the secretory
pathway, tethering secretory vesicles to the sites of exocytosis. Here, we discuss three independent
lines of evidence that indicate surprising genetic, physical and functional interactions between the two
complexes. Although much of the existing evidence is rather preliminary in nature, these interactions
might serve to coordinate the biosynthetic capacity of the cell with the function of the secretory
machinery.
Publication Types:
Review
PMID: 15106610 [PubMed - indexed for MEDLINE]
1: Nat Struct Mol Biol. 2005 Oct;12(10):879-85. Epub 2005 Sep 11.
Sec15 interacts with Rab11 via a novel domain and affects Rab11 localization in vivo.
Wu S, Mehta SQ, Pichaud F, Bellen HJ, Quiocho FA.
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of
Medicine, Houston, Texas 77030, USA.
Sec15, a component of the exocyst, recognizes vesicle-associated Rab GTPases, helps target
transport vesicles to the budding sites in yeast and is thought to recruit other exocyst proteins. Here
we report the characterization of a 35-kDa fragment that comprises most of the C-terminal half of
Drosophila melanogaster Sec15. This C-terminal domain was found to bind a subset of Rab GTPases,
especially Rab11, in a GTP-dependent manner. We also provide evidence that in fly photoreceptors
Sec15 colocalizes with Rab11 and that loss of Sec15 affects rhabdomere morphology. Determination
of the 2.5-A crystal structure of the C-terminal domain revealed a novel fold consisting of ten alphahelices equally distributed between two subdomains (N and C subdomains). We show that the C
subdomain, mainly via a single helix, is sufficient for Rab binding.
Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
PMID: 16155582 [PubMed - indexed for MEDLINE]
2: Dev Cell. 2005 Sep;9(3):355-76.
Drosophila exocyst components Sec5, Sec6, and Sec15 regulate DE-Cadherin trafficking from
recycling endosomes to the plasma membrane.
Langevin J, Morgan MJ, Sibarita JB, Aresta S, Murthy M, Schwarz T, Camonis J, Bellaiche Y.
Polarite Cellulaire chez la drosophile, UMR 144, Paris, France.
The E-Cadherin-catenin complex plays a critical role in epithelial cell-cell adhesion, polarization, and
morphogenesis. Here, we have analyzed the mechanism of Drosophila E-Cadherin (DE-Cad)
localization. Loss of function of the Drosophila exocyst components sec5, sec6, and sec15 in epithelial
cells results in DE-Cad accumulation in an enlarged Rab11 recycling endosomal compartment and
inhibits DE-Cad delivery to the membrane. Furthermore, Rab11 and Armadillo interact with the
exocyst components Sec15 and Sec10, respectively. Our results support a model whereby the
exocyst regulates DE-Cadherin trafficking, from recycling endosomes to sites on the epithelial cell
membrane where Armadillo is located.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 16224820 [PubMed - indexed for MEDLINE]
1: Nature. 2006 Dec 6; [Epub ahead of print]
A systems biology analysis of the Drosophila phagosome.
Stuart LM, Boulais J, Charriere GM, Hennessy EJ, Brunet S, Jutras I, Goyette G, Rondeau C, Letarte
S, Huang H, Ye P, Morales F, Kocks C, Bader JS, Desjardins M, Ezekowitz RA.
[1] Laboratory of Developmental Immunology, Massachusetts General Hospital/ Harvard Medical
School, 55 Fruit Street, Boston, Massachusetts 02114, USA [2] MRC Centre for Inflammation
Research, The University of Edinburgh, The Queen's Medical Research Institute, 47 Little France
Crescent, Edinburgh EH16 4TJ, UK.
Phagocytes have a critical function in remodelling tissues during embryogenesis and thereafter are
central effectors of immune defence. During phagocytosis, particles are internalized into
'phagosomes', organelles from which immune processes such as microbial destruction and antigen
presentation are initiated. Certain pathogens have evolved mechanisms to evade the immune system
and persist undetected within phagocytes, and it is therefore evident that a detailed knowledge of this
process is essential to an understanding of many aspects of innate and adaptive immunity. However,
despite the crucial role of phagosomes in immunity, their components and organization are not fully
defined. Here we present a systems biology analysis of phagosomes isolated from cells derived from
the genetically tractable model organism Drosophila melanogaster and address the complex dynamic
interactions between proteins within this organelle and their involvement in particle engulfment.
Proteomic analysis identified 617 proteins potentially associated with Drosophila phagosomes; these
were organized by protein-protein interactions to generate the 'phagosome interactome', a detailed
protein-protein interaction network of this subcellular compartment. These networks predicted both the
architecture of the phagosome and putative biomodules. The contribution of each protein and complex
to bacterial internalization was tested by RNA-mediated interference and identified known components
of the phagocytic machinery. In addition, the prediction and validation of regulators of phagocytosis
such as the 'exocyst', a macromolecular complex required for exocytosis but not previously implicated
in phagocytosis, validates this strategy. In generating this 'systems-based model', we show the power
of applying this approach to the study of complex cellular processes and organelles and expect that
this detailed model of the phagosome will provide a new framework for studying host-pathogen
interactions and innate immunity.
PMID: 17151602 [PubMed - as supplied by publisher]
3: Biochem Soc Trans. 2006 Nov;34(Pt 5):687-90.
The molecular mechanisms of the mammalian exocyst complex in exocytosis.
Wang S, Hsu SC.
Department of Cell Biology and Neuroscience, Rutgers University, Nelson Biological Laboratories, 604
Allison Rd, D419, Piscataway, NJ 08854, USA.
Exocytosis is a highly ordered vesicle trafficking pathway that targets proteins to the plasma
membrane for membrane addition or secretion. Research over the years has discovered many
proteins that participate at various stages in the mammalian exocytotic pathway. At the early stage of
exocytosis, co-atomer proteins and their respective adaptors and GTPases have been shown to play a
role in the sorting and incorporation of proteins into secretory vesicles. At the final stage of exocytosis,
SNAREs (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor) and SNAREassociated proteins are believed to mediate the fusion of secretory vesicles at the plasma membrane.
There are multiple events that may occur between the budding of secretory vesicles from the Golgi
and the fusion of these vesicles at the plasma membrane. The most obvious and best-known event is
the transport of secretory vesicles from Golgi to the vicinity of the plasma membrane via microtubules
and their associated motors. At the vicinity of the plasma membrane, however, it is not clear how
vesicles finally dock and fuse with the plasma membrane. Identification of proteins involved in these
events should provide important insights into the mechanisms of this little known stage of the
exocytotic pathway. Currently, a protein complex, known as the sec6/8 or the exocyst complex, has
been implicated to play a role at this late stage of exocytosis.
PMID: 17052175 [PubMed - in process]
4: Biochem Soc Trans. 2006 Nov;34(Pt 5):683-6.
Interactions between Rabs, tethers, SNAREs and their regulators in exocytosis.
Novick P, Medkova M, Dong G, Hutagalung A, Reinisch K, Grosshans B.
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA.
peter.novick@yale.edu
Sec2p is the exchange factor that activates Sec4p, the Rab GTPase controlling the final stage of the
yeast exocytic pathway. Sec2p is recruited to secretory vesicles by Ypt32-GTP, a Rab controlling exit
from the Golgi. Sec15p, a subunit of the octameric exocyst tethering complex and an effector of
Sec4p, binds to Sec2p on secretory vesicles, displacing Ypt32p. Sec2p mutants defective in the region
450-508 amino acids bind to Sec15p more tightly. In these mutants, Sec2p accumulates in the cytosol
in a complex with the exocyst and is not recruited to vesicles by Ypt32p. Thus the region 450-508
amino acids negatively regulates the association of Sec2p with the exocyst, allowing it to recycle on to
new vesicles. The structures of one nearly full-length exocyst subunit and three partial subunits have
been determined and, despite very low sequence identity, all form rod-like structures built of helical
bundles stacked end to end. These rods may bind to each other along their sides to form the
assembled complex. While Sec15p binds Sec4-GTP on the vesicle, other subunits bind Rho GTPases
on the plasma membrane, thus tethering vesicles to exocytic sites. Sec4-GTP also binds Sro7p, a
yeast homologue of the Drosophila lgl (lethal giant larvae) tumour suppressor. Sro7 also binds to
Sec9p, a SNAP25 (25 kDa synaptosome-associated protein)-like t-SNARE [target-membrane-
associated SNARE (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor)],
and can form a Sec4p-Sro7p-Sec9p ternary complex. Overexpression of Sec4p, Sro7p or Sec1p
(another SNARE regulator) can bypass deletions of three different exocyst subunits. Thus promoting
SNARE function can compensate for tethering defects.
PMID: 17052174 [PubMed - in process]
5: J Cell Biol. 2006 Jul 17;174(2):207-20.
Exit from mitosis triggers Chs2p transport from the endoplasmic reticulum to mother-daughter
neck via the secretory pathway in budding yeast.
Zhang G, Kashimshetty R, Ng KE, Tan HB, Yeong FM.
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore,
Singapore 117597.
Budding yeast chitin synthase 2 (Chs2p), which lays down the primary septum, localizes to the
mother-daughter neck in telophase. However, the mechanism underlying the timely neck localization
of Chs2p is not known. Recently, it was found that a component of the exocyst complex, Sec3p-green
fluorescent protein, arrives at the neck upon mitotic exit. It is not clear whether the neck localization of
Chs2p, which is a cargo of the exocyst complex, was similarly regulated by mitotic exit. We report that
Chs2p was restrained in the endoplasmic reticulum (ER) during metaphase. Furthermore, mitotic exit
was sufficient to cause Chs2p neck localization specifically by triggering the Sec12p-dependent
transport of Chs2p out of the ER. Chs2p was "forced" prematurely to the neck by mitotic kinase
inactivation at metaphase, with chitin deposition occurring between mother and daughter cells. The
dependence of Chs2p exit from the ER followed by its transport to the neck upon mitotic exit ensures
that septum formation occurs only after the completion of mitotic events.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 16847101 [PubMed - indexed for MEDLINE]
6: Nat Struct Mol Biol. 2006 Jul;13(7):577-81.
The exocyst defrocked, a framework of rods revealed.
Munson M, Novick P.
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical
School, 364 Plantation Street, Worcester, Massachusetts 01605, USA.
mary.munson@umassmed.edu
The exocyst complex is required for the interaction of vesicles with the plasma membrane in
preparation for exocytic fusion. Recent crystallographic studies indicate that at least four of the eight
subunits contain long, rod-like domains formed from helical bundles. These rods may pack against
one another to generate the framework of the complex. How this complex assembles, how it responds
to various GTPases and how it is ultimately displaced to allow bilayer fusion are key questions for the
future.
Publication Types:
Research Support, N.I.H., Extramural
Review
PMID: 16826234 [PubMed - indexed for MEDLINE]
7: Int J Biochem Cell Biol. 2006;38(11):1841-7. Epub 2006 May 9.
Ral: mediator of membrane trafficking.
van Dam EM, Robinson PJ.
Cell Signalling Unit, Children's Medical Research Institute, Locked Bag 23, Wentworthville, NSW
2145, Australia.
Ral is a multifunctional small GTPase involved in tumorigenesis and in controlling intracellular
membrane trafficking. It is mainly activated by factors downstream of Ras, or independently of these
factors and operates by protein-protein interactions with an expanding repertoire of partners. RalA is a
positive regulator of calcium-evoked exocytosis via binding phospholipase D and is involved in G
protein coupled receptor signalling by binding phospholipase C-delta1. The binding of Ral to
calmodulin links to intracellular trafficking events. Another link is direct binding of activated Ral (RalGTP) to the endocytic and exocytic machineries. Ral-GTP binds RalBP1, which connects to receptormediated endocytosis via AP-2. Alternatively, Ral-GTP binds the exocyst complex, which controls
secretory vesicle trafficking in regulated secretion and filopodia formation. Thus, Ral-GTP "chooses"
between different membrane trafficking pathways. Other Ral partners are still being uncovered that
may provide further mechanistic insights into how Ral controls diverse membrane trafficking pathways.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 16781882 [PubMed - indexed for MEDLINE]
8: Nat Struct Mol Biol. 2006 Jun;13(6):555-6. Epub 2006 May 14.
The structure of the exocyst subunit Sec6p defines a conserved architecture with diverse
roles.
Sivaram MV, Furgason ML, Brewer DN, Munson M.
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical
School, 364 Plantation Street, Worcester, Massachusetts 01605, USA.
The exocyst is a conserved protein complex essential for trafficking secretory vesicles to the plasma
membrane. The structure of the C-terminal domain of the exocyst subunit Sec6p reveals multiple
helical bundles, which are structurally and topologically similar to Exo70p and the C-terminal domains
of Exo84p and Sec15, despite <10% sequence identity. The helical bundles appear to be
evolutionarily related molecular scaffolds that have diverged to create functionally distinct exocyst
proteins.
Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
PMID: 16699513 [PubMed - indexed for MEDLINE]
1: EMBO J. 2006 Apr 19;25(8):1623-34. Epub 2006 Apr 6.
Dual role of the exocyst in AMPA receptor targeting and insertion into the postsynaptic
membrane.
Gerges NZ, Backos DS, Rupasinghe CN, Spaller MR, Esteban JA.
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109-0632,
USA.
Intracellular membrane trafficking of glutamate receptors at excitatory synapses is critical for synaptic
function. However, little is known about the specialized trafficking events occurring at the postsynaptic
membrane. We have found that two components of the exocyst complex, Sec8 and Exo70, separately
control synaptic targeting and insertion of AMPA-type glutamate receptors. Sec8 controls the
directional movement of receptors towards synapses through PDZ-dependent interactions. In contrast,
Exo70 mediates receptor insertion at the postsynaptic membrane, but it does not participate in
receptor targeting.
Thus, interference with Exo70 function accumulates AMPA receptors inside the spine, forming a
complex physically associated, but not yet fused with the postsynaptic membrane. Electron
microscopic analysis of these complexes indicates that Exo70 mediates AMPA receptor insertion
directly within the postsynaptic density, rather than at extrasynaptic membranes. Therefore, we
propose a molecular and anatomical model that dissects AMPA receptor sorting and synaptic delivery
within the spine, and uncovers new functions of the exocyst at the postsynaptic membrane.
PMID: 16601687 [PubMed - indexed for MEDLINE]