Structural Insights into Arl1-Mediated Targeting of the Arf-GEF BIG1 to the trans-Golgi

Galindo, Antonio; Soler, Nicolas; McLaughlin, Stephen H.; Yu, Myeong-Hee; Williams, Roger L.; Munro, Sean

doi:10.1016/j.celrep.2016.06.022

Cited by 30 publications

(37 citation statements)

References 61 publications

(92 reference statements)

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“…The Arf1-related GTPase Arl1 was shown to be necessary for the recruitment of BIG1 to the Golgi 42,43 and this is mediated by a direct interaction of Arl1-GTP with the DCB domain. 43 Another trafficking small GTPase, Rab1b, was required for the localization of GBF1 to the Golgi and was shown to interact with the DCB-HUS N-terminal domains. 44 Ypt1-GTP, the yeast ortholog of Rab1, Arl1-GTP and Ypt31-GTP, the yeast ortholog of Rab11, also bound to yeast Sec7.…”

Section: Regulation Of Large Arfgefs By Direct and Small Gtpase-mediamentioning

confidence: 99%

Allosteric regulation of Arf GTPases and their GEFs at the membrane interface

2016

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Arf GTPases assemble protein complexes on membranes to carry out major functions in cellular traffic. An essential step is their activation by guanine nucleotide exchange factors (GEFs), whose Sec7 domain stimulates GDP/GTP exchange. ArfGEFs form 2 major families: ArfGEFs with DCB, HUS and HDS domains (GBF1 and BIG1/BIG2 in humans), which act at the Golgi; and ArfGEFs with a Cterminal PH domain (cytohesin, EFA6 and BRAG), which function at the plasma membrane and endosomes. In addition, pathogenic bacteria encode an ArfGEF with a unique membrane-binding domain. Here we review the allosteric regulation of Arf GTPases and their GEFs at the membrane interface. Membranes contribute several regulatory layers: at the GTPase level, where activation by GTP is coupled to membrane recruitment by a built-in structural device; at the Sec7 domain, which manipulates this device to ensure that Arf-GTP is attached to membranes; and at the level of noncatalytic ArfGEF domains, which form direct or GTPase-mediated interactions with membranes that enable a spectacular diversity of regulatory regimes. Notably, we show here that membranes increase the efficiency of a large ArfGEF (human BIG1) by 32-fold by interacting directly with its Nterminal DCB and HUS domains. The diversity of allosteric regulatory regimes suggests that ArfGEFs can function in cascades and circuits to modulate the shape, amplitude and duration of Arf signals in cells. Because Arf-like GTPases feature autoinhibitory elements similar to those of Arf GTPases, we propose that their activation also requires allosteric interactions of these elements with membranes or other proteins.

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Section: Regulation Of Large Arfgefs By Direct and Small Gtpase-mediamentioning

confidence: 99%

Allosteric regulation of Arf GTPases and their GEFs at the membrane interface

2016

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“…cis-and trans-Golgi-localized guanine nucleotide exchange factors (GEFs) recruit and activate Arf1 by replacing GDP with GTP (Galindo et al, 2016;Gustafson and Fromme, 2017;Peyroche et al, 2001), which is catalysed by the conserved Sec7 domain (Mossessova et al, 1998). In its GTP-bound form, Arf1 inserts a myristoylated N-terminal amphipathic helix into the lipid bilayer (Antonny et al, 1997;Goldberg, 1998;Pasqualato et al, 2002).…”

Section: Membrane Recruitment Of Copi and Associated Machinerymentioning

confidence: 99%

Formation of COPI-coated vesicles at a glance

Arakel

Schwappach

2018

Journal of Cell Science

100

106

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“…Arrowheads point to the GST fusion proteins used in pulldowns. Breakdown products of GBF1 DCB-HUS were also observed by Galindo et al (2016). Sec7-HDS1 is partially obscured by the BSA present in all samples.…”

Section: Discussionmentioning

confidence: 76%

“…GST DCB-HUS pulled down Arf4, bound to GTPγS or GDPβS, whereas Sec7-HDS1 preferably interacted with GDPβS-bound Arf4. To ascertain that GBF1 DCB-HUS is properly folded and binds rhodopsin specifically, we used Arl1 as a negative control, as its binding to the DCB domain is conserved in BIG1 and BIG2, but not in GBF1 (Christis and Munro, 2012;Galindo et al, 2016). We incubated purified bovine rhodopsin, or Arl1Q71L, with increasing amounts of GBF1 DCB-HUS bound to glutathione beads.…”

Section: Gbf1 Directly Interacts With Arf4 and The Ciliary Cargo Rhomentioning

confidence: 99%

The Arf GEF GBF1 and Arf4 synergize with the sensory receptor cargo, rhodopsin, to regulate ciliary membrane trafficking

Wang

Fresquez

Kandachar

et al. 2017

Journal of Cell Science

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The small GTPase Arf4 and the Arf GTPase-activating protein (GAP) ASAP1 cooperatively sequester sensory receptor cargo into transport carriers targeted to primary cilia, but the input that drives Arf4 activation in this process remains unknown. Here, we show, by using frog retinas and recombinant human proteins, that during the carrier biogenesis from the photoreceptor Golgi/trans-Golgi network (TGN) a functional complex is formed between Arf4, the Arf guanine nucleotide exchange factor (GEF) GBF1 and the light-sensing receptor, rhodopsin. Rhodopsin and Arf4 bind the regulatory Nterminal dimerization and cyclophillin-binding (DCB)-homology upstream of Sec7 (HUS) domain of GBF1. The complex is sensitive to Golgicide A (GCA), a selective inhibitor of GBF1 that accordingly blocks rhodopsin delivery to the cilia, without disrupting the photoreceptor Golgi. The emergence of newly synthesized rhodopsin in the endomembrane system is essential for GBF1-Arf4 complex formation in vivo. Notably, GBF1 interacts with the Arf GAP ASAP1 in a GCA-resistant manner. Our findings indicate that converging signals on GBF1 from the influx of cargo into the Golgi/ TGN and the feedback from Arf4, combined with input from ASAP1, control Arf4 activation during sensory membrane trafficking to primary cilia.

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Structural Insights into Arl1-Mediated Targeting of the Arf-GEF BIG1 to the trans-Golgi

Cited by 30 publications

References 61 publications

Allosteric regulation of Arf GTPases and their GEFs at the membrane interface

Allosteric regulation of Arf GTPases and their GEFs at the membrane interface

Formation of COPI-coated vesicles at a glance

The Arf GEF GBF1 and Arf4 synergize with the sensory receptor cargo, rhodopsin, to regulate ciliary membrane trafficking

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