Syt1p promotes activation of Arl1p at the late Golgi to recruit Imh1p

Chen, Kuan‐Yu; Tsai, Pei-Chin; Hsu, Jong-Ping; Hsu, Hsin-Chia; Fang, Chiung-Ying; Chang, Lin-Chun; Tsai, Yu‐Chuan; Yu, Chia‐Jung; Lee, Fang‐Jen S.

doi:10.1242/jcs.074237

Cited by 25 publications

(55 citation statements)

References 71 publications

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“…S2 F and G). This finding is consistent with our previous reports that Gea2p is not required for the Golgi targeting of Arl1p (29). Together, these results indicate that Arl1p and Drs2p or Gea2p partially colocalize at the TGN, but their targeting to the TGN is not dependent on one another.…”

Section: Resultssupporting

confidence: 93%

Arl1p regulates spatial membrane organization at the trans -Golgi network through interaction with Arf-GEF Gea2p and flippase Drs2p

Tsai

Hsu

Liu

et al. 2013

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

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Significance Membrane asymmetry, curvature, and dynamics have major roles in cellular processes, including vesicle transport. The GTPase ADP ribosylation factor (Arf) and a lipid translocase (flippase) are critical for membrane reorganization during vesicle formation. Direct evidence that Arf and flippase work in concert on membrane transformation/architecture is, however, lacking. We demonstrate that activated Arf-like protein Arl1 interacts with the Arf-activating guanine nucleotide-exchange factor Gea2 and flippase Drs2, forming a ternary complex that is required for lipid asymmetry and Arl1 function at the Golgi. These findings represent a previously missing piece of the puzzle that is our understanding of Arf-mediated membrane remodeling.

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Section: Resultssupporting

confidence: 93%

Arl1p regulates spatial membrane organization at the trans -Golgi network through interaction with Arf-GEF Gea2p and flippase Drs2p

Tsai

Hsu

Liu

et al. 2013

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

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“…The GTP-bound active form Arl1p associates with Golgi membranes, whereas the GDP-bound inactive form is distributed in the cytosol. To determine whether the diffuse distribution of Arl1p in imh1D cells was a result of the reduction of GTP-bound Arl1p in the cell, we measured the amount of active Arl1p in wild-type and imh1D cells using an Imh1p pull-down assay (Chen et al, 2010). The C-terminal region of Imh1p (GST-Imh1-C177) binds specifically to the active form of Arl1p but not to the inactive form of Arl1p.…”

Section: Deletion Of Imh1 Results In Decreased Gtp-bound Arl1pmentioning

confidence: 99%

“…In yeast, the GEF Syt1p activates a subset of Arl1p, and the ARFGAP Gcs1p regulates its GTP hydrolysis (Chen et al, 2010;Liu et al, 2005). In addition to the GAP and GEF, another Arl protein, Arl3p, also play an upstream role to regulate activation and Golgi localization of Arl1p.…”

Section: Introductionmentioning

confidence: 99%

“…It has been suggested that ArfGAP1, a membrane curvature sensitive GAP, controls the binding of golgins to active Arf1 or Arl1 through its GTP hydrolysis stimulating activity (Bigay et al, 2005;Drin et al, 2008). Similarly, yeast Gcs1p, an ortholog of ArfGAP1, also contains a membrane curvature sensitive ALPS motif (Bigay et al, 2005) and regulates the Imh1p Golgi targeting through the stimulation of Arl1p GTP hydrolysis (Chen et al, 2010;Liu et al, 2005). However, the mechanism by which Gcs1p accesses the GTP-bound form of Arl1p on the TGN and stimulates GTP hydrolysis has not been explored.…”

Section: Introductionmentioning

confidence: 99%

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Competition between the golgin Imh1p and the Gcs1p GAP stabilizes activated Arl1p at the late-Golgi

Chen

Tsai

Liu

et al. 2012

Journal of Cell Science

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SummaryGolgins play diverse roles in regulating the structure and function of the Golgi. The yeast golgin Imh1p is targeted to the trans-Golgi network (TGN) through interaction of its GRIP domain with GTP-bound Arl1p. Recycling of Arl1p and Imh1p to the cytosol requires the hydrolysis of GTP bound to Arl1p; however, the point at which GTP hydrolysis occurs remains unknown. Here, we report that selfinteraction of Imh1p plays a role in modulating spatial inactivation of Arl1p. Deletion of IMH1 in yeast decreases the amount of the GTP-bound Arl1p and results in less Arl1p residing on the TGN. Biochemically, purified Imh1p competes with Gcs1p, an Arl1p GTPase-activating protein (GAP), for binding to Arl1p, thus interfering with the GAP activity of Gcs1p toward Arl1p. Furthermore, we demonstrate that the self-interaction of Imh1p attenuates the Gcs1p-dependent GTP hydrolysis of Arl1p. Thus, we propose that the golgin Imh1p serves as a feedback regulator to modulate the GTP hydrolysis of Arl1p.

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“…For example Syt1p has a Sec7‐homology guanine exchange factor (GEF) domain, and related GEFs in other species have a classical PH domain. The non‐significant hit in Syt1p (E‐values: SMART = 0.002, Pfam not found (>10), SuperFamily = 0.05) has been accepted as PH‐like, because the GEF domain homology strongly enhances the likelihood of a PH‐like domain existing 43, 44…”

Section: Profile‐sequence Tools Currently Used To Define Domainsmentioning

confidence: 99%

Using HHsearch to tackle proteins of unknown function: A pilot study with PH domains

Fidler¹,

Murphy²,

Courtis³

et al. 2016

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Advances in membrane cell biology are hampered by the relatively high proportion of proteins with no known function. Such proteins are largely or entirely devoid of structurally significant domain annotations. Structural bioinformaticians have developed profile‐profile tools such as HHsearch (online version called HHpred), which can detect remote homologies that are missed by tools used to annotate databases. Here we have applied HHsearch to study a single structural fold in a single model organism as proof of principle. In the entire clan of protein domains sharing the pleckstrin homology domain fold in yeast, systematic application of HHsearch accurately identified known PH‐like domains. It also predicted 16 new domains in 13 yeast proteins many of which are implicated in intracellular traffic. One of these was Vps13p, where we confirmed the functional importance of the predicted PH‐like domain. Even though such predictions require considerable work to be corroborated, they are useful first steps. HHsearch should be applied more widely, particularly across entire proteomes of model organisms, to significantly improve database annotations.

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Syt1p promotes activation of Arl1p at the late Golgi to recruit Imh1p

Cited by 25 publications

References 71 publications

Arl1p regulates spatial membrane organization at the trans -Golgi network through interaction with Arf-GEF Gea2p and flippase Drs2p

Arl1p regulates spatial membrane organization at the trans -Golgi network through interaction with Arf-GEF Gea2p and flippase Drs2p

Competition between the golgin Imh1p and the Gcs1p GAP stabilizes activated Arl1p at the late-Golgi

Using HHsearch to tackle proteins of unknown function: A pilot study with PH domains

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