Mutational analysis of SEC4 suggests a cyclical mechanism for the regulation of vesicular traffic.

Walworth, Nancy C.; Goud, Bruno; Kabcenell, Alisa K.; Novick, Peter

doi:10.1002/j.1460-2075.1989.tb03560.x

Cited by 310 publications

(229 citation statements)

References 39 publications

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“…These observations contrast with those of several other GTPases, such as Ras, Rab5, and Rab7, whose function is augmented by expression of "dominant-active" GTPase hydrolysis mutants, resulting in a phenotype opposite that of cells expressing the "dominant-negative" GTPbinding mutant (Barbacid, 1987;Stenmark et al, 1994;Bucci et al, 2000). However, in this respect Rab10 is similar to the closely related Sec4p, whose function is inhibited by overexpression of either the GTP-binding or GTP-hydrolysis mutants (Walworth et al, 1989(Walworth et al, , 1992. Thus unlike Ras, the function of Rab10 and Sec4p may not depend upon the level of the GTP-bound form so much as upon a cycle of GTP binding and hydrolysis.…”

Section: Mechanism Of the Inhibitory Effects Of Mutant Forms Of Gfp-rmentioning

confidence: 73%

“…The corresponding mutations in Ras, Rab7, Rab8, Rab11a, and Rab25 have been shown to decrease the affinity of the protein for GTP, resulting in the accumulation of a GDP-bound form (Feig and Cooper, 1988;Peranen et al, 1996;Bucci et al, 2000;Wang et al, 2000). This mutation frequently results in a protein with dominant-negative effects on Rab function; overexpression has been found to alter the function of Rab8 (Moritz et al, 2001) and yeast Sec4p (Walworth et al, 1989), as well as Rab4 (McCaffrey et al, 2001), Rab5 , Rab7 (Feng et al, 1995;Bucci et al, 2000), Rab11 (Ullrich et al, 1996;Wang et al, 2000a), Rab14 (Jununtula et al, 2004), and Rab15 (Zuk and Elferink, 2000). A second mutant was also created, encoding a change from glutamine into leucine at position 68 (Q68L).…”

Section: Mutations In the Gtp-binding And Gtp-hydrolysis Domains Altementioning

confidence: 99%

“…This subfamily of Rabs represents the closest mammalian relatives of the Sec4p (Chen et al, 1993;Pereira-Leal and Seabra, 2001), one of the first described Rab proteins, which mediates polarized transport from the trans-Golgi network (TGN) to the site of bud formation in yeast (Salminen and Novick, 1987;Walworth et al, 1989). Like Sec4p, Rab8 and Rab13 have also been associated with polarized membrane transport.…”

Section: Introductionmentioning

confidence: 99%

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Rab10 Regulates Membrane Transport through Early Endosomes of Polarized Madin-Darby Canine Kidney Cells

Babbey

Ahktar

Wang

et al. 2006

MBoC

155

129

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Section: Mechanism Of the Inhibitory Effects Of Mutant Forms Of Gfp-rmentioning

confidence: 73%

Section: Mutations In the Gtp-binding And Gtp-hydrolysis Domains Altementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Rab10 Regulates Membrane Transport through Early Endosomes of Polarized Madin-Darby Canine Kidney Cells

Babbey

Ahktar

Wang

et al. 2006

MBoC

155

129

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“…Alternatively, if regulation of CK1 activity occurs, it may be through posttranslational modification, through association with other polypeptides (e.g., a regulatory subunit), or through limitation of its access to physiological substrates by changes in its subcellular distribution. Regarding this last possibility, it has been proposed that the membrane association of other CC motif-containing proteins (YPT1 and SEC4) is reversible (Walworth et al, 1989). The predicted mass of yeast CK1 (:62 kDa) is larger than the 54-kDa protein we purified at the outset (Kuret, A M 1 2 unpublished data).…”

Section: Discussionmentioning

confidence: 86%

Two genes in Saccharomyces cerevisiae encode a membrane-bound form of casein kinase-1.

Wang

Vančura

Mitcheson

et al. 1992

MBoC

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Two cDNAs encoding casein kinase-1 have been isolated from a yeast cDNA library and termed CKI1 and CKI2. Each clone encodes a protein of approximately 62,000 Da containing a highly conserved protein kinase domain surrounded by variable amino- and carboxy-terminal domains. The proteins also contain two conserved carboxy-terminal cysteine residues that comprise a consensus sequence for prenylation. Consistent with this posttranslational modification, cell fractionation experiments demonstrate that intact CKI1 is found exclusively in yeast cell membranes. Gene disruption experiments reveal that, although neither of the two CKI genes is essential by itself, at least one CKI gene is required for yeast cell viability. Spores deficient in both CKI1 and CKI2 fail to grow and, therefore, either fail to germinate or arrest as small cells before bud emergence. These results suggest that casein kinase-1, which is distributed widely in nature, plays a pivotal role in eukaryotic cell regulation.

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“…Our results thus suggest that the association of Mso1p with Sec1p is not regulated by the GTPase activity of Sec4p. Sec4-8p binds poorly GTP, Sec4N34 binds preferentially GDP, whereas Sec4I133p is presumably defective both in GDP and GTP binding (Walworth et al, 1989). Although, Sec4N34p and I133 mutants bind similarly the Sec4p function regulating proteins Sec2p and Dss1p Walch-Solimena et al, 1997), these mutants are likely to posses slightly different conformations due to their different nucleotide binding properties.…”

Section: Discussionmentioning

confidence: 99%

Molecular Interactions Position Mso1p, a Novel PTB Domain Homologue, in the Interface of the Exocyst Complex and the Exocytic SNARE Machinery in Yeast

Knop

Miller

Mazza

et al. 2005

MBoC

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In this study, we have analyzed the association of the Sec1p interacting protein Mso1p with the membrane fusion machinery in yeast. We show that Mso1p is essential for vesicle fusion during prospore membrane formation. Green fluorescent protein-tagged Mso1p localizes to the sites of exocytosis and at the site of prospore membrane formation. In vivo and in vitro experiments identified a short amino-terminal sequence in Mso1p that mediates its interaction with Sec1p and is needed for vesicle fusion. A point mutation, T47A, within the Sec1p-binding domain abolishes Mso1p functionality in vivo, and mso1T47A mutant cells display specific genetic interactions with sec1 mutants. Mso1p coimmunoprecipitates with Sec1p, Sso1/2p, Snc1/2p, Sec9p, and the exocyst complex subunit Sec15p. In sec4-8 and SEC4I133 mutant cells, association of Mso1p with Sso1/2p, Snc1/2p, and Sec9p is affected, whereas interaction with Sec1p persists. Furthermore, in SEC4I133 cells the dominant negative Sec4I133p coimmunoprecipitates with Mso1p-Sec1p complex. Finally, we identify Mso1p as a homologue of the PTB binding domain of the mammalian Sec1p binding Mint proteins.These results position Mso1p in the interface of the exocyst complex, Sec4p, and the SNARE machinery, and reveal a novel layer of molecular conservation in the exocytosis machinery. INTRODUCTIONEvolutionarily conserved molecular machinery regulates transport vesicle targeting, tethering, and fusion in eukaryotic cells. In yeast Saccharomyces cerevisiae this machinery involves the activity of the eight-subunit (Sec3p, Sec5p, Sec6p, Sec8p, Sec10p, Sec15p, Exo70p, and Exo84p) tethering complex, the exocyst, a rab family small GTPase Sec4p, and the exocytic SNARE complex (Snc1/2p, Sec9p, and Sso1/2p) thought to drive the actual lipid bilayer fusion . The exocyst subunit Sec15p has been shown to act as an effector for Sec4p (Guo et al., 1999). In addition, sec4-8 mutant cells are defective in Snc1/2p-Sec9p-Sso1/2p SNARE complex assembly (Carr et al., 1999). Despite these and numerous other studies, the regulatory mechanisms for SNARE complex formation are still poorly understood. The Sec1/Munc18 (SM) protein family members represent central regulators of SNARE complex function. These proteins perform an essential, albeit currently poorly understood function in SNARE complex regulation (Gallwitz and Jahn, 2003;Toonen and Verhage, 2003;Kauppi et al., 2004).Yeast S. cerevisiae possesses four Sec1p-family proteins: Sec1p mediates vesicle fusion at the plasma membrane (Novick et al., 1981;Carr et al., 1999), Sly1p mediates vesicle fusion at the endoplasmic reticulum-Golgi interface (Ossig et al., 1991), Vps33p is required for endosome to vacuole transport and vacuole maintenance (Banta et al., 1990), and Vps45p mediates Golgi-to-vacuole transport (Piper et al., 1994;Cowles et al., 1994). Sec1p is the closest homologue of the mammalian Munc18-1 that has been shown to associate with syntaxin 1 and to regulate the syntaxin 1-synaptobrevin-SNAP-25 SNARE complex assembly (Misura et al., 2000;Kaup...

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Mutational analysis of SEC4 suggests a cyclical mechanism for the regulation of vesicular traffic.

Cited by 310 publications

References 39 publications

Rab10 Regulates Membrane Transport through Early Endosomes of Polarized Madin-Darby Canine Kidney Cells

Rab10 Regulates Membrane Transport through Early Endosomes of Polarized Madin-Darby Canine Kidney Cells

Two genes in Saccharomyces cerevisiae encode a membrane-bound form of casein kinase-1.

Molecular Interactions Position Mso1p, a Novel PTB Domain Homologue, in the Interface of the Exocyst Complex and the Exocytic SNARE Machinery in Yeast

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