scholarly journals Intersectin-1 interacts with the golgin GCC88 to couple the actin network and Golgi architecture

2019 ◽  
Vol 30 (3) ◽  
pp. 370-386 ◽  
Author(s):  
Christian Makhoul ◽  
Prajakta Gosavi ◽  
Regina Duffield ◽  
Bronwen Delbridge ◽  
Nicholas A. Williamson ◽  
...  
Keyword(s):  
Dynamic Balance ◽  
Nucleotide Exchange ◽  
Actin Networks ◽  
Guanine Nucleotide Exchange ◽  
Membrane Flux ◽  
Nucleotide Exchange Factor ◽  
Golgi Ribbon ◽  
Microtubule Networks ◽  
Golgi Network ◽  
Membrane Tether

The maintenance of the Golgi ribbon relies on a dynamic balance between the actin and microtubule networks; however, the pathways controlling actin networks remain poorly defined. Previously, we showed that the trans-Golgi network (TGN) membrane tether/golgin, GCC88, modulates the Golgi ribbon architecture. Here, we show that dispersal of the Golgi ribbon by GCC88 is dependent on actin and the involvement of nonmuscle myosin IIA. We have identified the long isoform of intersectin-1 (ITSN-1), a guanine nucleotide exchange factor for Cdc42, as a novel Golgi component and an interaction partner of GCC88 responsible for mediating the actin-dependent dispersal of the Golgi ribbon. We show that perturbation of Golgi morphology by changes in membrane flux, mediated by silencing the retromer subunit Vps26, or in a model of neurodegeneration, induced by Tau overexpression, are also dependent on the ITSN-1-GCC88 interaction. Overall, our study reveals a role for a TGN golgin and ITSN-1 in linking to the actin cytoskeleton and regulating the balance between a compact Golgi ribbon and a dispersed Golgi, a pathway with relevance to pathophysiological conditions.

Activation of ADP-ribosylation factor regulates biogenesis of the ATP7A-containing trans-Golgi network compartment and its Cu-induced trafficking

2007 ◽  
Vol 293 (6) ◽  
pp. C1753-C1767 ◽  
Author(s):  
Zoe G. Holloway ◽  
Robert Grabski ◽  
Tomasz Szul ◽  
Melanie L. Styers ◽  
Julie A. Coventry ◽  
...  
Keyword(s):  
Brefeldin A ◽  
Nucleotide Exchange ◽  
Adp Ribosylation ◽  
Trans Golgi Network ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Inactive Form ◽  
Golgi Ribbon ◽  
Golgi Network ◽  
Adp Ribosylation Factor

ATP7A (MNK) regulates copper homeostasis by translocating from a compartment localized within the trans-Golgi network to the plasma membrane (PM) in response to increased copper load. The mechanisms that regulate the biogenesis of the MNK compartment and the trafficking of MNK are unclear. Here we show that the architecture of the MNK compartment is linked to the structure of the Golgi ribbon. Depletion of p115 tethering factor, which causes fragmentation of the Golgi ribbon, also disrupts the MNK compartment. In p115-depleted cells, MNK localizes to punctate structures that pattern on Golgi ministacks dispersed throughout the cell. Despite altered localization MNK trafficking still occurs, and MNK relocates from and returns to the fragmented compartment in response to copper. We further show that the biogenesis of the MNK compartment requires activation of ADP-ribosylation factor (Arf)1 GTPase, shown previously to facilitate the biogenesis of the Golgi ribbon. Activation of cellular Arf1 is prevented by 1) expressing an inactive “empty” form of Arf (Arf1/N126I), 2) expressing an inactive form of GBF1 (GBF1/E794K), guanine nucleotide exchange factor for Arf1, or 3) treating cells with brefeldin A, an inhibitor of GBF1 that disrupts MNK into a diffuse pattern. Importantly, preventing Arf activation inhibits copper-responsive trafficking of MNK to the PM. Our findings support a model in which active Arf is essential for the generation of the MNK compartment and for copper-responsive trafficking of MNK from there to the PM. Our findings provide an exciting foundation for identifying Arf1 effectors that facilitate the biogenesis of the MNK compartment and MNK traffic.

scholarly journals Promiscuity of the catalytic Sec7 domain within the guanine nucleotide exchange factor GBF1 in ARF activation, Golgi homeostasis, and effector recruitment

2019 ◽  
Vol 30 (12) ◽  
pp. 1523-1535 ◽  
Author(s):  
Jay M. Bhatt ◽  
William Hancock ◽  
Justyna M. Meissner ◽  
Aneta Kaczmarczyk ◽  
Eunjoo Lee ◽  
...  
Keyword(s):  
Brefeldin A ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factors ◽  
Downstream Effector ◽  
Nucleotide Exchange Factor ◽  
Sec7 Domain ◽  
Golgi Network ◽  
The Impact

The integrity of the Golgi and trans-Golgi network (TGN) is disrupted by brefeldin A (BFA), which inhibits the Golgi-localized BFA-sensitive factor (GBF1) and brefeldin A–inhibited guanine nucleotide-exchange factors (BIG1 and BIG2). Using a cellular replacement assay to assess GBF1 functionality without interference from the BIGs, we show that GBF1 alone maintains Golgi architecture; facilitates secretion; activates ADP-ribosylation factor (ARF)1, 3, 4, and 5; and recruits ARF effectors to Golgi membranes. Unexpectedly, GBF1 also supports TGN integrity and recruits numerous TGN-localized ARF effectors. The impact of the catalytic Sec7 domain (Sec7d) on GBF1 functionality was assessed by swapping it with the Sec7d from ARF nucleotide-binding site opener (ARNO)/cytohesin-2, a plasma membrane GEF reported to activate all ARFs. The resulting chimera (GBF1-ARNO-GBF1 [GARG]) targets like GBF1, supports Golgi/TGN architecture, and facilitates secretion. However, unlike GBF1, GARG activates all ARFs (including ARF6) at the Golgi/TGN and recruits additional ARF effectors to the Golgi/TGN. Our results have general implications: 1) GEF’s targeting is independent of Sec7d, but Sec7d influence the GEF substrate specificity and downstream effector events; 2) all ARFs have access to all membranes, but are restricted in their distribution by the localization of their activating GEFs; and 3) effector association with membranes requires the coincidental presence of activated ARFs and specific membrane identifiers.

scholarly journals Golgi-localized LOT regulates trans-Golgi network biogenesis and pollen tube growth

2018 ◽  
Vol 115 (48) ◽  
pp. 12307-12312 ◽  
Author(s):  
Peng-Fei Jia ◽  
Yong Xue ◽  
Hong-Ju Li ◽  
Wei-Cai Yang
Keyword(s):  
Pollen Tube ◽  
Pollen Tube Growth ◽  
Tube Growth ◽  
Molecular Regulation ◽  
Rab Gtpase ◽  
Nucleotide Exchange ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Localization Analysis ◽  
Golgi Network

The trans-Golgi network (TGN) is an essential tubular-vesicular organelle derived from the Golgi and functions as an independent sorting and trafficking hub within the cell. However, the molecular regulation of TGN biogenesis remains enigmatic. Here we identified an Arabidopsis mutant loss of TGN (lot) that is defective in TGN formation and sterile due to impaired pollen tube growth in the style. The mutation leads to overstacking of the Golgi cisternae and significant reduction in the number of TGNs and vesicles surrounding the Golgi in pollen, which is corroborated by the dispersed cytosolic distribution of TGN-localized proteins. Consistently, deposition of extracellular pectin and plasma membrane localization of kinases and phosphoinositide species are also impaired. Subcellular localization analysis suggests that LOT is localized on the periphery of the Golgi cisternae, but the mutation does not affect the localization of Golgi-resident proteins. Furthermore, the yeast complementation result suggests that LOT could functionally act as a component of the guanine nucleotide exchange factor (GEF) complex of small Rab GTPase Ypt6. Taken together, these findings suggest that LOT is a critical player for TGN biogenesis in the plant lineage.

scholarly journals Rab GTPase regulation of retromer-mediated cargo export during endosome maturation

2012 ◽  
Vol 23 (13) ◽  
pp. 2505-2515 ◽  
Author(s):  
Ting-Ting Liu ◽  
Timothy S. Gomez ◽  
Bridget K. Sackey ◽  
Daniel D. Billadeau ◽  
Christopher G. Burd
Keyword(s):  
Yeast Cells ◽  
Rab Gtpase ◽  
Nucleotide Exchange ◽  
Dual Roles ◽  
Sorting Nexin ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Golgi Network ◽  
Endosome Maturation

The retromer complex, composed of sorting nexin subunits and a Vps26/Vps29/Vps35 trimer, mediates sorting of retrograde cargo from the endosome to the trans-Golgi network. The retromer trimer subcomplex is an effector of Rab7 (Ypt7 in yeast). Whereas endosome targeting of human retromer has been shown to require Rab7-GTP, targeting of yeast retromer to the endosome is independent of Ypt7-GTP and requires the Vps5 and Vps17 retromer sorting nexin subunits. An evolutionarily conserved amino acid segment within Vps35 is required for Ypt7/Rab7 recognition in vivo by both yeast and human retromer, establishing that Rab recognition is a conserved feature of this subunit. Recognition of Ypt7 by retromer is required for its function in retrograde sorting, and in yeast cells lacking the guanine nucleotide exchange factor for Ypt7, retrograde cargo accumulates in endosomes that are decorated with retromer, revealing an additional role for Rab recognition at the cargo export stage of the retromer functional cycle. In addition, yeast retromer trimer antagonizes Ypt7-regulated organelle tethering and fusion of endosomes/vacuoles via recognition of Ypt7. Thus retromer has dual roles in retrograde cargo export and in controlling the fusion dynamics of the late endovacuolar system.

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