A ras-like protein is required for a post-Golgi event in yeast secretion

Salminen, Antti; Novick, Peter

doi:10.1016/0092-8674(87)90455-7

Cited by 846 publications

(517 citation statements)

References 41 publications

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“…WT (n ϭ 32), aex-6(sa24) (n ϭ 9), rab-3(js49) (n ϭ 16), T. R. Mahoney et al 1993;Sollner, 2003;Sudhof, 2004). The yeast exocytic Rab Sec4 is required for exocytosis (Salminen and Novick, 1987). Surprisingly, knockout of Rab3, an exocytic Rab, in mice and rab-3 mutant C. elegans exhibit only a mild decrease in synaptic transmission Schluter et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Synaptic Transmission by RAB-3 and RAB-27 inCaenorhabditis elegans

Mahoney

Liu

Itoh

et al. 2006

MBoC

165

218

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Rab small GTPases are involved in the transport of vesicles between different membranous organelles. RAB-3 is an exocytic Rab that plays a modulatory role in synaptic transmission. Unexpectedly, mutations in the Caenorhabditis elegans RAB-3 exchange factor homologue, aex-3, cause a more severe synaptic transmission defect as well as a defecation defect not seen in rab-3 mutants. We hypothesized that AEX-3 may regulate a second Rab that regulates these processes with RAB-3. We found that AEX-3 regulates another exocytic Rab, RAB-27. Here, we show that C. elegans RAB-27 is localized to synapse-rich regions pan-neuronally and is also expressed in intestinal cells. We identify aex-6 alleles as containing mutations in rab-27. Interestingly, aex-6 mutants exhibit the same defecation defect as aex-3 mutants. aex-6; rab-3 double mutants have behavioral and pharmacological defects similar to aex-3 mutants. In addition, we demonstrate that RBF-1 (rabphilin) is an effector of RAB-27. Therefore, our work demonstrates that AEX-3 regulates both RAB-3 and RAB-27, that both RAB-3 and RAB-27 regulate synaptic transmission, and that RAB-27 potentially acts through its effector RBF-1 to promote soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) function. INTRODUCTIONNeurotransmitter release is accomplished by the fusion of neurotransmitter-filled synaptic vesicles at the presynaptic nerve terminal. This process occurs through a series of highly regulated steps that include synaptic vesicle transport, docking/tethering, priming, fusion, endocytosis, recycling, and neurotransmitter refilling (Sudhof, 2004). Several genes have been assigned roles in the various steps of the synaptic vesicle cycle. Rab3 (termed RAB-3 in Caenorhabditis elegans), a member of the Rab family of small GTPases, regulates synaptic transmission, possibly through the docking, priming, or fusion steps Schluter et al., 2004).Rabs act in a variety of cell types and regulate vesicular transport between organelles. Rabs cycle on and off membranes via a GTP-dependent mechanism (Zerial and McBride, 2001). Rab activity is regulated by two proteins, which act in an antagonistic manner. The guanine nucleotide exchange factor (GEF) exchanges GTP for GDP, and the GTPase activating protein activates the intrinsic GTPase activity of a Rab (Bernards, 2003). GDP bound Rabs are held off of the membrane by a GDP dissociation inhibitor (Wu et al., 1996). The GTP/membrane-bound form of Rabs typically binds to a variety of effectors that regulate particular steps of membrane transport and cell signaling (Zerial and McBride, 2001;Spang, 2004).Rab3 was once thought to play a central role in regulating release. However, recent work has shown that a quadruple knockout of all four isoforms of Rab3 in mice only results in a 30% reduction in evoked synaptic response (Schluter et al., 2004). This is consistent with work in C. elegans showing that mutations in the single rab-3 gene cause only mild defects in synaptic transmission . Surprisingly, more dramatic phe...

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Section: Discussionmentioning

confidence: 99%

Regulation of Synaptic Transmission by RAB-3 and RAB-27 inCaenorhabditis elegans

Mahoney

Liu

Itoh

et al. 2006

MBoC

165

218

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“…Among proteins critical for the fusion of secretory vesicles with the plasma membrane are the rab-GTPase Sec4p (Salminen and Novick, 1987), its guanine-nucleotideexchange-factor Sec2p (Walch-Solimena et al, 1997), and a protein complex termed the exocyst (composed of Sec3p, 5p, 6p, 8p, 10p, 15p, Exo70p, and Exo84p) (TerBush and Novick, 1995;TerBush et al, 1996;Guo et al, 1999). Temperaturesensitive mutations of these result in accumulation of postGolgi secretory vesicles and an exocytic block at restrictive temperatures (Novick et al, 1980(Novick et al, , 1981Guo et al, 1999).…”

Section: Polarized Secretion Maintains Cable Assembly Activity At Thementioning

confidence: 99%

Stable and Dynamic Axes of Polarity Use Distinct Formin Isoforms in Budding Yeast

Pruyne

Gao

et al. 2004

MBoC

151

208

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Bud growth in yeast is guided by myosin-driven delivery of secretory vesicles from the mother cell to the bud. We find transport occurs along two sets of actin cables assembled by two formin isoforms. The Bnr1p formin assembles cables that radiate from the bud neck into the mother, providing a stable mother-bud axis. These cables also depend on septins at the neck and are required for efficient transport from the mother to the bud. The Bni1p formin assembles cables that line the bud cortex and target vesicles to varying locations in the bud. Loss of these cables results in morphological defects as vesicles accumulate at the neck. Assembly of these cables depends on continued polarized secretion, suggesting vesicular transport provides a positive feedback signal for Bni1p activation, possibly by rho-proteins. By coupling different formin isoforms to unique cortical landmarks, yeast uses common cytoskeletal elements to maintain stable and dynamic axes in the same cell. INTRODUCTIONProper cell polarization requires a balance between dynamism and stability. Persistent systems, such as the apical and basolateral domains of epithelial cells, show a higher stability than flexible systems, such as cells undergoing chemotaxis. However, both types can use similar cytoskeletal components, so an important task in understanding the control of polarity is to identify features that influence persistence, and how those features integrate with the core cytoskeletal machinery providing the physical expression of polarity.The process of bud growth of the yeast Saccharomyces cerevisiae provides a model for examining the control of polarity (for reviews, see Bretscher, 2003;Chang and Peter, 2003). Secretory organelles, such as the Golgi and endoplasmic reticulum, are distributed throughout the bud and mother cell, whereas post-Golgi secretory vesicles concentrate at discrete growth sites at the cell cortex. These vesicles are guided to these sites along what are essentially two axes of polarity: a stable axis directing traffic from the mother into the bud, and a dynamic axis that fine-tunes delivery from the bud neck to specific regions in the bud, sending vesicles first to the small bud tip, then to the entire bud surface, and finally back toward the neck during mother/daughter separation. On delivery to these locations, post-Golgi vesicles fuse with the cell surface to promote localized cell expansion.Two class-V myosins, with heavy chains encoded by MYO2 (Johnston et al., 1991) and MYO4 (Haarer et al., 1994), propel cellular components, including vesicles, organelles, mRNAs, and microtubules, from the mother into the bud during growth and organelle segregation. The myosins move along cables of actin filaments that radiate throughout the cell in arrays oriented toward growth sites (Adams and Pringle, 1984;Kilmartin and Adams, 1984).Assembly of these cables depends on two formin homologues, Bni1p and Bnr1p (Evangelista et al., 2002;Sagot et al., 2002a), members of a family of cytoskeletal regulatory proteins defined by conserved fo...

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“…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%

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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A ras-like protein is required for a post-Golgi event in yeast secretion

Cited by 846 publications

References 41 publications

Regulation of Synaptic Transmission by RAB-3 and RAB-27 inCaenorhabditis elegans

Regulation of Synaptic Transmission by RAB-3 and RAB-27 inCaenorhabditis elegans

Stable and Dynamic Axes of Polarity Use Distinct Formin Isoforms in Budding Yeast

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

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