The Golgin Tether Giantin Regulates the Secretory Pathway by Controlling Stack Organization within Golgi Apparatus

Koreishi, Mayuko; Gniadek, Thomas J.; Yu, Sidney; Masuda, Junko; Honjo, Yasuko; Satoh, Ayano

doi:10.1371/journal.pone.0059821

Cited by 69 publications

(79 citation statements)

References 32 publications

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“…As the staining pattern for MFSD14A revealed a more condensed intracellular localization, co-staining with intracellular organelle markers for Golgi was performed. Anti-Giantin antibody, targeting a protein located in the cisterna of the Golgi apparatus (Linstedt and Hauri, 1993; Koreishi et al, 2013), overlapped well with MFSD14A staining ( Figure 6B ). Since MFSD14B had a more spread out staining pattern, co-staining with an anti-KDEL antibody was performed.…”

Section: Resultsmentioning

confidence: 76%

Putative Membrane-Bound Transporters MFSD14A and MFSD14B Are Neuronal and Affected by Nutrient Availability

Lekholm

Perland

Eriksson

et al. 2017

Front. Mol. Neurosci.

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Characterization of orphan transporters is of importance due to their involvement in cellular homeostasis but also in pharmacokinetics and pharmacodynamics. The tissue and cellular localization, as well as function, is still unknown for many of the solute carriers belonging to the major facilitator superfamily (MFS) Pfam clan. Here, we have characterized two putative novel transporters MFSD14A (HIAT1) and MFSD14B (HIATL1) in the mouse central nervous system and found protein staining throughout the adult mouse brain. Both transporters localized to neurons and MFSD14A co-localized with the Golgi marker Giantin in primary embryonic cortex cultures, while MFSD14B staining co-localized with an endoplasmic retention marker, KDEL. Based on phylogenetic clustering analyses, we predict both to have organic substrate profiles, and possible involvement in energy homeostasis. Therefore, we monitored gene regulation changes in mouse embryonic primary cultures after amino acid starvations and found both transporters to be upregulated after 3 h of starvation. Interestingly, in mice subjected to 24 h of food starvation, both transporters were downregulated in the hypothalamus, while Mfsd14a was also downregulated in the brainstem. In addition, in mice fed a high fat diet (HFD), upregulation of both transporters was seen in the striatum. Both MFSD14A and MFSD14B were intracellular neuronal membrane-bound proteins, expressed in the Golgi and Endoplasmic reticulum, affected by both starvation and HFD to varying degree in the mouse brain.

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Section: Resultsmentioning

confidence: 76%

Putative Membrane-Bound Transporters MFSD14A and MFSD14B Are Neuronal and Affected by Nutrient Availability

Lekholm

Perland

Eriksson

et al. 2017

Front. Mol. Neurosci.

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“…This unique structure suggested that it might play a role in vesicle tethering to the Golgi membranes in conjunction with p115 and GM130, another p115-interacting golgin (Alvarez et al, 2001;Lesa et al, 2000;Linstedt et al, 2000;Sönnichsen et al, 1998). Whereas several other golgins, as well as p115, have been shown to be essential for Golgi structural integrity in siRNA knockdown studies in cell culture assays, knockdown of Golgb1 mRNAs or protein did not cause disruption of Golgi structures or reassembly following mitosis (Koreishi et al, 2013;Puthenveedu and Linstedt, 2001). Recently, Kim et al generated mice heterozygous for Uso1, encoding the p115 protein, and confirmed genetically that p115 function is required for Golgi structural integrity and cell survival (Kim et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Golgb1 has been found to interact with the transcytosis-associated protein p115 (also known as Uso1), a cytosolic protein involved in tethering endoplasmic reticulum (ER)-derived vesicles to the Golgi in mammalian cells as well as in yeast (Cao et al, 1998;Koreishi et al, 2013;Puthenveedu and Linstedt, 2001). Mouse embryos deficient in p115 exhibit early embryonic lethality and Golgi fragmentation in trophoblast cells (Kim et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Golgb1 regulates protein glycosylation and is crucial for mammalian palate development

et al. 2016

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Cleft palate is a common major birth defect for which currently known causes account for less than 30% of pathology in humans. In this study, we carried out mutagenesis screening in mice to identify new regulators of palatogenesis. Through genetic linkage mapping and whole exome sequencing, we identified a loss-of-function mutation in the Golgb1 gene that co-segregated with cleft palate in a new mutant mouse line. Golgb1 encodes a ubiquitously expressed large coiled-coil protein, known as giantin, that is localized at the Golgi membrane. Using CRISPR/Cas9-mediated genome editing, we generated and analyzed developmental defects in mice carrying additional Golgb1 loss-of-function mutations, which validated a critical requirement for Golgb1 in palate development. Through maxillary explant culture assays, we demonstrate that the Golgb1 mutant embryos have intrinsic defects in palatal shelf elevation. Just prior to the developmental stage of palatal shelf elevation in the wildtype littermates, Golgb1 mutant embryos exhibit increased cell density, reduced hyaluronan accumulation, and impaired protein glycosylation in the palatal mesenchyme. Together, these results demonstrate that, although it is a ubiquitously expressed Golgi-associated protein, Golgb1 has specific functions in protein glycosylation and tissue morphogenesis.

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“…Giantin is a resident Golgi protein that is anchored to the membrane of Golgi. It forms a complex with other Golgi proteins, such as p115 and Rab1, and regulates vesicle tethering and fusion processes in the Golgi apparatus (44). We used Giantin-RLuc8 as a localization marker to examine PAR 2 -induced translocation of G␤␥ to the Golgi compartment.…”

Section: Pkd Mediates Par 2 Translocation From the Golgi Apparatus Tomentioning

confidence: 99%

Protein Kinase D and Gβγ Subunits Mediate Agonist-evoked Translocation of Protease-activated Receptor-2 from the Golgi Apparatus to the Plasma Membrane

Jensen

Zhao

Jiménez-Vargas

et al. 2016

Journal of Biological Chemistry

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Agonist-evoked endocytosis of G protein-coupled receptors has been extensively studied. The mechanisms by which agonists stimulate mobilization and plasma membrane translocation of G protein-coupled receptors from intracellular stores are unexplored. Protease-activated receptor-2 (PAR 2 ) traffics to lysosomes, and sustained protease signaling requires mobilization and plasma membrane trafficking of PAR 2 from Golgi stores. We evaluated the contribution of protein kinase D (PKD) and G␤␥ to this process. In HEK293 and KNRK cells, the PAR 2 agonists trypsin and 2-furoyl-LIGRLO-NH 2 activated PKD in the Golgi apparatus, where PKD regulates protein trafficking. PAR 2 activation induced translocation of G␤␥, a PKD activator, to the Golgi apparatus, determined by bioluminescence resonance energy transfer between G␥-Venus and giantin-Rluc8. Inhibitors of PKD (CRT0066101) and G␤␥ (gallein) prevented PAR 2 -stimulated activation of PKD. CRT0066101, PKD1 siRNA, and gallein all inhibited recovery of PAR 2 -evoked Ca 2؉ signaling. PAR 2 with a photoconvertible Kaede tag was expressed in KNRK cells to examine receptor translocation from the Golgi apparatus to the plasma membrane. Irradiation of the Golgi region (405 nm) induced green-red photo-conversion of PAR 2 -Kaede. Trypsin depleted PAR 2 -Kaede from the Golgi apparatus and repleted PAR 2 -Kaede at the plasma membrane. CRT0066101 inhibited PAR 2 -Kaede translocation to the plasma membrane. CRT0066101 also inhibited sustained protease signaling to colonocytes and nociceptive neurons that naturally express PAR 2 and mediate protease-evoked inflammation and nociception. Our results reveal a major role for PKD and G␤␥ in agonist-evoked mobilization of intracellular PAR 2 stores that is required for sustained signaling by extracellular proteases.

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The Golgin Tether Giantin Regulates the Secretory Pathway by Controlling Stack Organization within Golgi Apparatus

Cited by 69 publications

References 32 publications

Putative Membrane-Bound Transporters MFSD14A and MFSD14B Are Neuronal and Affected by Nutrient Availability

Putative Membrane-Bound Transporters MFSD14A and MFSD14B Are Neuronal and Affected by Nutrient Availability

Golgb1 regulates protein glycosylation and is crucial for mammalian palate development

Protein Kinase D and Gβγ Subunits Mediate Agonist-evoked Translocation of Protease-activated Receptor-2 from the Golgi Apparatus to the Plasma Membrane

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