Rab1b overexpression modifies Golgi size and gene expression in HeLa cells and modulates the thyrotrophin response in thyroid cells in culture

Roméro, N.; Dumur, Catherine I.; Martinez, Hernán; García, Iris Alejandra; Monetta, Pablo Miguel; Slavin, Ileana; Sampieri, Luciana; Koritschoner, Nicolás P.; Mirоnоv, Alexander A.; Matteis, Maria Antonietta De; Álvarez, Cecilia

doi:10.1091/mbc.e12-07-0530

Cited by 22 publications

(20 citation statements)

References 55 publications

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“…Previous studies have described a crucial role for RAB1B in maintaining Golgi structure and function (Romero et al, 2013). The Golgi network consists of stacks of membrane-bound structures.…”

Section: Resultsmentioning

confidence: 99%

PITPNC1 Recruits RAB1B to the Golgi Network to Drive Malignant Secretion

et al. 2016

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SUMMARY Enhanced secretion of tumorigenic effector proteins is a feature of malignant cells. The molecular and cellular mechanisms underlying this feature are poorly defined. We identify PITPNC1 as a gene amplified in a large fraction of human breast cancer and over-expressed in metastatic breast, melanoma and colon cancer. Biochemical, molecular, and cell-biological studies reveal that PITPNC1 promotes malignant secretion by binding Golgi resident PI4P and localizing RAB1B to the Golgi. RAB1B localization to the Golgi allows for the recruitment of GOLPH3 to the trans-Golgi, which facilitates Golgi extension and enhanced vesicular release. PITPNC1-mediated vesicular release drives metastasis by increasing the secretion of pro-invasive and pro-angiogenic mediators HTRA1, MMP1, FAM3C, PDGFA, and ADAM10. We establish PITPNC1 as a PI4P-binding protein that enhances vesicular secretion capacity in malignancy.

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Section: Resultsmentioning

confidence: 99%

PITPNC1 Recruits RAB1B to the Golgi Network to Drive Malignant Secretion

et al. 2016

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“…Interestingly, increased Rab1b expression causes increased expression of GalT and other Golgi-associated proteins. These increases are accompanied by elongation of the Golgi cisternae and a pronounced accumulation of round to irregular shaped membrane structures at what is probably the trans side of the Golgi cisternal stack (Romero et al, 2013). The outcome of more recent screening studies supports the conclusion that Rab1 either directly or indirectly is very important to Golgi organization.…”

Section: Rab Proteins Fall Into Two Major Functional/phenotypic CLmentioning

confidence: 99%

How Rab Proteins Determine Golgi Structure

Liu

Storrie

2015

International Review of Cell and Molecular Biology

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Rab proteins, small GTPases, are key regulators of mammalian Golgi apparatus organization. Based on the effect of Rab activation state, Rab proteins fall into two functional classes. In Class1, inactivation induces Golgi ribbon fragmentation and/or redistribution of Golgi enzymes to the ER, while overexpression of wild type or activation has little, if any, effect on Golgi ribbon organization. In Class 2, the reverse is true. We give emphasis to Rab6, the most abundant Golgi-associated Rab protein. Rab6 depletion in HeLa cells causes an increase in Golgi cisternal number, longer, more continuous cisternae, and a pronounced accumulation of vesicles; the effect of Rab6 on Golgi ribbon organization is probably through regulation of vesicle transport. In effector studies, motor proteins and their regulators are found to be key Rab6 effectors. A related Rab, Rab41, affects Golgi ribbon organization in a contrasting manner. The balance between minus- and plus-end directed motor recruitment may well be the major Rab-dependent factor in Golgi ribbon organization.

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“…As discussed previously, RAB1B directly binds GBF1 and promotes GBF1 recruitment to membranes. However, RAB1B also has transcriptional effects: overexpression of RAB1 in HeLa cells coordinately induced enlargement of the Golgi and up-regulated mRNA levels of GBF1 and numerous other traffic regulators such as KDELR3 and GM130 [159]. The signaling pathway responsible for this induction requires the activity of the p38 mitogen-activated protein kinase and the cAMP-responsive element-binding protein consensus binding site in promoter regions of the target genes.…”

Section: Effects Of Cell Physiology On Gef Functionmentioning

confidence: 99%

Regulating the large Sec7 ARF guanine nucleotide exchange factors: the when, where and how of activation

Wright

Kahn

Sztul

2014

Cell. Mol. Life Sci.

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Eukaryotic cells require selective sorting and transport of cargo between intracellular compartments. This is accomplished at least in part by vesicles that bud from a donor compartment, sequestering a subset of resident protein “cargos” destined for transport to an acceptor compartment. A key step in vesicle formation and targeting is the recruitment of specific proteins that form a coat on the outside of the vesicle in a process requiring the activation of regulatory GTPases of the ARF family. Like all such GTPases, ARFs cycle between inactive, GDP-bound, and membrane-associated active, GTP-bound, conformations. And like most regulatory GTPases the activating step is slow and thought to be rate limiting in cells, requiring the use of ARF guanine nucleotide exchange factor (GEFs). ARF GEFs are characterized by the presence of a conserved, catalytic Sec7 domain, though they also contain motifs or additional domains that confer specificity to localization and regulation of activity. These domains have been used to define and classify five different sub-families of ARF GEFs. One of these, the BIG/GBF1 family, includes three proteins that are each key regulators of the secretory pathway. GEF activity initiates the coating of nascent vesicles via the localized generation of activated ARFs and thus these GEFs are the upstream regulators that define the site and timing of vesicle production. Paradoxically, while we have detailed molecular knowledge of how GEFs activate ARFs, we know very little about how GEFs are recruited and/or activated at the right time and place to initiate transport. This review summarizes the current knowledge of GEF regulation and explores the still uncertain mechanisms that position GEFs at “budding ready” membrane sites to generate highly localized activated ARFs.

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Rab1b overexpression modifies Golgi size and gene expression in HeLa cells and modulates the thyrotrophin response in thyroid cells in culture

Cited by 22 publications

References 55 publications

PITPNC1 Recruits RAB1B to the Golgi Network to Drive Malignant Secretion

PITPNC1 Recruits RAB1B to the Golgi Network to Drive Malignant Secretion

How Rab Proteins Determine Golgi Structure

Regulating the large Sec7 ARF guanine nucleotide exchange factors: the when, where and how of activation

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