Dual Prenylation Is Required for Rab Protein Localization and Function

Calero, Monica; Chen, Catherine Z.; Wen-yan, Zhu; Winand, Nena J.; Havas, Karyn A.; Gilbert, Penney M.; Burd, Christopher G.; Collins, Ruth

doi:10.1091/mbc.e02-11-0707

Cited by 122 publications

(108 citation statements)

References 57 publications

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“…2C). GFP-Ypt1 localizes to multiple puncta per cell (26). Previously published studies of intracellular localization of Trs85 tagged with GFP or 3×GFP were inconclusive (17,27).…”

Section: Resultsmentioning

confidence: 95%

Regulation of selective autophagy onset by a Ypt/Rab GTPase module

Lipatova¹,

Belogortseva

Zhang³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

118

180

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The key regulators of intracellular trafficking, Ypt/Rab GTPases, are stimulated by specific upstream activators and, when activated, recruit specific downstream effectors to mediate membrane-transport events. The yeast Ypt1 and its human functional homolog hRab1 regulate both endoplasmic reticulum (ER)-to-Golgi transport and autophagy. However, it is not clear whether the mechanism by which these GTPases regulate autophagy depends on their well-documented function in ER-to-Golgi transport. Here, we identify Atg11, the preautophagosomal structure (PAS) organizer, as a downstream effector of Ypt1 and show that the Ypt1-Atg11 interaction is required for PAS assembly under normal growth conditions. Moreover, we show that Ypt1 and Atg11 colocalize with Trs85, a Ypt1 activator subunit, and together they regulate selective autophagy. Finally, we show that Ypt1 and Trs85 interact on Atg9-containing membranes, which serve as a source for the membrane component of the PAS. Together our results define a Ypt/Rab module-comprising an activator, GTPase, and effector-that orchestrates the onset of selective autophagy, a process vital for cell homeostasis. Furthermore, because Atg11 does not play a role in ER-to-Golgi transport, we demonstrate here that Ypt/Rabs can regulate two independent membrane-transport processes by recruiting process-specific effectors.

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“…2C). GFP-Ypt1 localizes to multiple puncta per cell (26). Previously published studies of intracellular localization of Trs85 tagged with GFP or 3×GFP were inconclusive (17,27).…”

Section: Resultsmentioning

confidence: 95%

Regulation of selective autophagy onset by a Ypt/Rab GTPase module

Lipatova¹,

Belogortseva

Zhang³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

118

180

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“…As a marker of secretory vesicles, we expressed GFP-Sec4p under its endogenous promoter. In wild-type cells, GFP-Sec4p localized to the bud tip or incipient bud site ( Figure 4A; Calero et al, 2003). In contrast, in ptc1⌬ cells, GFP-Sec4p was mis-localized ( Figure 4A).…”

Section: Ptc1 Regulates the Distribution Of Several Cargoesmentioning

confidence: 97%

PTC1Is Required for Vacuole Inheritance and Promotes the Association of the Myosin-V Vacuole-specific Receptor Complex

Jin

Eves

Tang

et al. 2009

MBoC

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Organelle inheritance occurs during cell division. In Saccharomyces cerevisiae, inheritance of the vacuole, and the distribution of mitochondria and cortical endoplasmic reticulum are regulated by Ptc1p, a type 2C protein phosphatase. Here we show that PTC1/VAC10 controls the distribution of additional cargoes moved by a myosin-V motor. These include peroxisomes, secretory vesicles, cargoes of Myo2p, and ASH1 mRNA, a cargo of Myo4p. We find that Ptc1p is required for the proper distribution of both Myo2p and Myo4p. Surprisingly, PTC1 is also required to maintain the steady-state levels of organelle-specific receptors, including Vac17p, Inp2p, and Mmr1p, which attach Myo2p to the vacuole, peroxisomes, and mitochondria, respectively. Furthermore, Vac17p fused to the cargo-binding domain of Myo2p suppressed the vacuole inheritance defect in ptc1⌬ cells. These findings suggest that PTC1 promotes the association of myosin-V with its organelle-specific adaptor proteins. Moreover, these observations suggest that despite the existence of organelle-specific receptors, there is a higher order regulation that coordinates the movement of diverse cellular components. INTRODUCTIONDuring each cell cycle, cytoplasmic organelles are actively distributed between dividing cells to maintain organelle copy number and volume. The yeast Saccharomyces cerevisiae is an excellent model system for studying the spatial and temporal control of organelle inheritance. In yeast, several organelles are transmitted from mother to daughter cells. These include the vacuole, mitochondria, the endoplasmic reticulum (ER), late-Golgi elements and peroxisomes (reviewed in Weisman, 2006).Early in the cell cycle, a portion of each organelle is transported into the emerging bud. The polarized transport of most organelles from the mother to the bud is an active process that requires the actin cytoskeleton, myosin-V motors, and receptor proteins, which physically connect the motor to organelle cargoes (Beach et al., 2000;Yin et al., 2000;Boldogh et al., 2001;Barr, 2002;Bretscher, 2003;Du et al., 2004;Fagarasanu et al., 2006bFagarasanu et al., , 2007Weisman, 2006). Thus, formation of a complex between the motor and receptor protein is important for polarized organelle transport.Similar to yeast, in vertebrates, myosin-V motors move cargoes along the actin cytoskeleton. The best studied cargo of vertebrate myosin-V are melanosomes, which are moved in melanocytes by myosin-Va. Melanosomes attach to myosin-Va through Rab27a and melanophilin (Fukuda and Kuroda, 2002;Wu et al., 2002). Rab27a, through geranylgeranylation, attaches to the melanosome membrane, and melanophilin connects myosin-Va and Rab27a. Myosin-V-based intracellular movement has been analyzed in many other eukaryotes, including frogs, fish, mammals, and plants; plant myosin-XI is the functional homologue of yeast and vertebrate myosin-V ( Kinkema and Schiefelbein, 1994;Provance and Mercer, 1999;Tuma and Gelfand, 1999;Desnos et al., 2007;Li and Nebenfuhr, 2007;Sheets et al., 2007;Shimmen, 2007).Ge...

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“…Several Rabs were found at the ER if they could not be delivered to the appropriate membrane. Interestingly, the ER also constitutes the target organelle for monoprenylated Rabs (47,50) and chimeric Rab proteins (51,52). We do not yet know if the ER localization is also important during the normal lifetime of Rabs, although it shows that a large fraction of Rabs do not remain cytoplasmic if the GEF is missing.…”

Section: Gfp-ypt7mentioning

confidence: 99%

Guanine Nucleotide Exchange Factors (GEFs) Have a Critical but Not Exclusive Role in Organelle Localization of Rab GTPases

Cabrera

Ungermann

2013

Journal of Biological Chemistry

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Background: Rab localization has been ascribed to guanine nucleotide exchange factor (GEF) localization. Results: GEF deletions result in mislocalization of Rabs to other membranes, which can be bypassed by a Rab mutant. Conclusion: GEFs are critical for Rab localization, but Rabs also have a GEF-independent ability to localize correctly. Significance: Our data reveal that both GEFs and Rabs contribute to Rab localization in cells.

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Dual Prenylation Is Required for Rab Protein Localization and Function

Cited by 122 publications

References 57 publications

Regulation of selective autophagy onset by a Ypt/Rab GTPase module

Regulation of selective autophagy onset by a Ypt/Rab GTPase module

PTC1Is Required for Vacuole Inheritance and Promotes the Association of the Myosin-V Vacuole-specific Receptor Complex

Guanine Nucleotide Exchange Factors (GEFs) Have a Critical but Not Exclusive Role in Organelle Localization of Rab GTPases

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