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Olivier Devergne, Gina H Sun, Trudi Schüpbach
The basement membrane (BM), a sheet of extracellular matrix lining the basal side of epithelia, is essential for epithelial cell function and integrity, yet the mechanisms that control the basal restriction of BM proteins are poorly understood. In epithelial cells, a specialized pathway is dedicated to restrict the deposition of BM proteins basally. Here, we report the identification of a factor in this pathway, a homolog of the mammalian guanine nucleotide exchange factor (GEF) Mss4, which we have named Stratum...
February 21, 2017: Cell Reports
Ya-Han Ting, Ting-Jun Lu, Arlen W Johnson, Jing-Ting Shie, Bo-Ru Chen, Suresh Kumar S, Kai-Yin Lo
Eukaryotic ribosomes are composed of rRNAs and ribosomal proteins. Ribosomal proteins are translated in the cytoplasm and imported into the nucleus for assembly with the rRNAs. It has been shown that chaperones or karyopherins responsible for import can maintain the stability of ribosomal proteins by neutralizing unfavorable positive charges and thus facilitate their transports. Among 79 ribosomal proteins in yeast, only a few are identified with specific chaperones. Besides the classic role in maintaining protein stability, chaperones have additional roles in transport, chaperoning the assembly site, and dissociation of ribosomal proteins from karyopherins...
January 13, 2017: Journal of Biological Chemistry
Linda van den Berg, Bernd U Koelsch, Bettina Winzen-Reichert, Christine Fischer, Andrea Kutritz, Andrea Kindler-Röhrborn
The incidence of neural tumors is sexually dimorphic in both, humans and rodents. The identification of genetic determinants contributing to sex-biased tumor development is an essential prerequisite for differential tumor prevention in males and females. F2 hybrids of inbred BDIV and BDIX rats, resistant and susceptible, respectively, to ethylnitrosourea-induced malignant peripheral nerve sheath tumors (MPNST) display a marked sex bias regarding tumor risk. Homozygous BDIV alleles at the Mss4 locus (90.9-111...
May 1, 2015: International Journal of Cancer. Journal International du Cancer
Lizhen Wu, Dijin Xu, Linkang Zhou, Bingxian Xie, Li Yu, Hongyuan Yang, Lei Huang, Jing Ye, Haiteng Deng, Y Adam Yuan, Shuai Chen, Peng Li
Rab GTPases, by targeting to specific membrane compartments, play essential roles in membrane trafficking. Lipid droplets (LDs) are dynamic subcellular organelles whose growth is closely linked to obesity and hepatic steatosis. Fsp27 is shown to be required for LD fusion and growth by enriching at LD-LD contact sites. Here, we identify Rab8a as a direct interactor and regulator of Fsp27 in mediating LD fusion in adipocytes. Knockdown of Rab8a in the livers of ob/ob mice results in the accumulation of smaller LDs and lower hepatic lipid levels...
August 25, 2014: Developmental Cell
Michael A Kennedy, Kenneth Gable, Karolina Niewola-Staszkowska, Susana Abreu, Anne Johnston, Linda J Harris, Fulvio Reggiori, Robbie Loewith, Teresa Dunn, Steffany A L Bennett, Kristin Baetz
Unbiased lipidomic approaches have identified impairments in glycerophosphocholine second messenger metabolism in patients with Alzheimer's disease. Specifically, we have shown that amyloid-β42 signals the intraneuronal accumulation of PC(O-16:0/2:0) which is associated with neurotoxicity. Similar to neuronal cells, intracellular accumulation of PC(O-16:0/2:0) is also toxic to Saccharomyces cerevisiae, making yeast an excellent model to decipher the pathological effects of this lipid. We previously reported that phospholipase D, a phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2)-binding protein, was relocalized in response to PC(O-16:0/2:0), suggesting that this neurotoxic lipid may remodel lipid signaling networks...
January 2014: PLoS Genetics
Isabelle Guillas, Aurélia Vernay, Jean-Jacques Vitagliano, Robert A Arkowitz
Phosphatidylinositol phosphates are important regulators of processes such as the cytoskeleton organization, membrane trafficking and gene transcription, which are all crucial for polarized cell growth. In particular, phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] has essential roles in polarized growth as well as in cellular responses to stress. In the yeast Saccharomyces cerevisiae, the sole phosphatidylinositol-4-phosphate 5-kinase (PI4P5K) Mss4p is essential for generating plasma membrane PtdIns(4,5)P2...
August 15, 2013: Journal of Cell Science
Robert Amson, Salvatore Pece, Jean-Christophe Marine, Pier Paolo Di Fiore, Adam Telerman
Evolutionary conserved and pleiotropic, the TPT1/TCTP gene (translationally controlled tumor protein, also called HRF, fortilin), encodes a highly structured mRNA shielded by ribonucleoproteins and closely resembling viral particles. This mRNA activates, as do viruses, protein kinase R (PKR). The TPT1/TCTP protein is structurally similar to mRNA-helicases and MSS4. TPT1/TCTP has recently been identified as a prognostic factor in breast cancer and a critical regulator of the tumor suppressor p53 and of the cancer stem cell (SC) compartment...
January 2013: Trends in Cell Biology
Yidi Sun, David G Drubin
Anionic phospholipids PI(4,5)P2 and phosphatidylserine (PS) are enriched in the cytosolic leaflet of the plasma membrane where endocytic sites form. In this study, we investigated the roles of PI(4,5)P2 and PS in clathrin-mediated endocytosis (CME) site initiation and vesicle formation in Saccharomyces cerevisiae. Live-cell imaging of endocytic protein dynamics in an mss4(ts) mutant, which has severely reduced PI(4,5)P2 levels, revealed that PI(4,5)P2 is required for endocytic membrane invagination but is less important for endocytic site initiation...
December 15, 2012: Journal of Cell Science
Ke Wang, Zhifen Yang, Xu Liu, Kai Mao, Usha Nair, Daniel J Klionsky
Macroautophagy (hereafter autophagy) is a degradative cellular pathway that protects eukaryotic cells from stress, starvation, and microbial infection. This process must be tightly controlled because too little or too much autophagy can be deleterious to cellular physiology. The phosphatidylinositol (PtdIns) 3-kinase Vps34 is a lipid kinase that regulates autophagy, but the role of other PtdIns kinases has not been examined. Here we demonstrate a role for PtdIns 4-kinases and PtdIns4P 5-kinases in selective and nonselective types of autophagy in yeast...
November 2, 2012: Journal of Biological Chemistry
Aurélia Vernay, Sébastien Schaub, Isabelle Guillas, Martine Bassilana, Robert A Arkowitz
Membrane lipids have been implicated in many critical cellular processes, yet little is known about the role of asymmetric lipid distribution in cell morphogenesis. The phosphoinositide bis-phosphate PI(4,5)P(2) is essential for polarized growth in a range of organisms. Although an asymmetric distribution of this phospholipid has been observed in some cells, long-range gradients of PI(4,5)P(2) have not been observed. Here, we show that in the human pathogenic fungus Candida albicans a steep, long-range gradient of PI(4,5)P(2) occurs concomitant with emergence of the hyphal filament...
August 20, 2012: Journal of Cell Biology
Yading Ling, Christopher J Stefan, Jason A Macgurn, Anjon Audhya, Scott D Emr
Phosphatidylinositol-4,5-bisphosphate, PtdIns(4,5)P(2), is an essential signalling lipid that regulates key processes such as endocytosis, exocytosis, actin cytoskeletal organization and calcium signalling. Maintaining proper levels of PtdIns(4,5)P(2) at the plasma membrane (PM) is crucial for cell survival and growth. We show that the conserved PtdIns(4)P 5-kinase, Mss4, forms dynamic, oligomeric structures at the PM that we term PIK patches. The dynamic assembly and disassembly of Mss4 PIK patches may provide a mechanism to precisely modulate Mss4 kinase activity, as needed, for localized regulation of PtdIns(4,5)P(2) synthesis...
June 29, 2012: EMBO Journal
B M Walter, C Nordhoff, G Varga, G Goncharenko, S W Schneider, S Ludwig, V Wixler
Mss4 (mammalian suppressor of Sec4) is an evolutionarily highly conserved protein and shows high sequence and structural similarity to nucleotide exchange factors. Although Mss4 tightly binds a series of exocytic Rab GTPases, it exercises only a low catalytic activity. Therefore Mss4 was proposed to work rather as a chaperone, protecting nucleotide free Rabs from degradation than as a nucleotide exchange factor. Here we provide further evidence for chaperone-like properties of Mss4. We show that expression levels of cellular Mss4 mRNA and protein are rapidly changed in response to a broad range of extracellular stress stimuli...
April 12, 2012: Cell Death & Disease
Ju-Suk Nam, Haijie Yang, Nam-Ho Kim, Yuanjie Sun, Byung-Soo Choi, Sung-Oh Huh
Foxg1 (previously named BF1) is a winged-helix transcription factor with restricted expression pattern in the telencephalic neuroepithelium of the neural tube and in the anterior half of the developing optic vesicle. Previous studies have shown that the targeted disruption of the Foxg1 gene leads to hypoplasia of the cerebral hemispheres with severe defect in the structures of the ventral telencephalon. To further investigate the molecular mechanisms by which Foxg1 plays essential roles during brain development, we have adopted a strategy to isolate genes whose expression changes immediately after introduction of Foxg1 in cultured neural precursor cell line, HiB5...
September 2010: Experimental Neurobiology
Chitra Kamble, Sandhya Jain, Erin Murphy, Kyoungtae Kim
Eisosomes are large immobile assemblies at the cortex of a cell under the membrane compartment of Can1 (MCC) in yeast. Slm1 has recently been identified as an MCC component that acts downstream of Mss4 in a pathway that regulates actin cytoskeleton organization in response to stress. In this study, we showed that inactivation of Slm proteins disrupts proper localization of the primary eisosome marker Pil1, providing evidence that Slm proteins play a role in eisosome organization. Furthermore, we found that slm ts mutant cells exhibit actin defects in both the ability to polarize cortical F-actin and the formation of cytoplasmic actin cables even at the permissive temperature (30 degrees C)...
March 2011: Journal of Biosciences
Fernando Cardona, Helena Orozco, Sylvie Friant, Agustín Aranda, Marcel lí del Olmo
SPI1 is a gene whose expression responds to many environmental stimuli, including entry into stationary phase. We have performed a screening to identify genes that activate SPI1 promoter when overexpressed. The phosphatidylinositol-4-phosphate 5-kinase gene MSS4 was identified as a positive activator of SPI1. Another SPI1 transcriptional regulator isolated was the flavodoxin-like gene YCP4. YCP4 and its homolog RFS1 regulate the expression of many genes during the late stages of growth. The double deletion mutant in YCP4 and its homolog RFS1 has an impact on gene expression related to metabolism by increasing the expression of genes involved in hexose transport and glycolysis, and decreasing expression of genes of amino acid metabolism pathways...
July 2011: Archives of Microbiology
Bernd Koelsch, Bettina Winzen-Reichert, Christine Fischer, Andrea Kutritz, Linda van den Berg, Andrea Kindler-Röhrborn
We previously mapped several gene loci influencing cancer risk of inbred BDIV and BDIX rats, resistant and susceptible, respectively, to N-ethyl-N-nitrosourea (ENU)-induced malignant peripheral nerve sheath tumors (MPNSTs). On the basis of a genomewide association analysis using a (BDIV × BDIX) F(2) generation the Mss4 locus on rat chromosome 6 was predicted to mediate resistance to MPNST development in the trigeminal nerves, preferentially in females. F(2) females homozygous for D6Mit1 proved almost exclusively resistant to peripheral neurooncogenesis, with no effect detectable in males...
May 1, 2011: Physiological Genomics
Viktor Wixler, Ludmilla Wixler, Anika Altenfeld, Stephan Ludwig, Roger S Goody, Aymelt Itzen
The Mss4 (mammalian suppressor of yeast Sec4) is an evolutionarily highly conserved protein and is expressed in all mammalian tissues. Although its precise biological function is still elusive, it has been shown to associate with a subset of secretory Rab proteins (Rab1b, Rab3a, Rab8a, Rab10) and to possess a rather low guanine nucleotide exchange factor (GEF) activity towards them in vitro (Rab1, Rab3a and Rab8a). By screening a human placenta cDNA library with Mss4 as bait, we identified several Rab GTPases (Rab12, Rab13 and Rab18) as novel Mss4-binding Rab proteins...
March 2011: Biological Chemistry
J C Price
On 15 Mar. 1984, during the initial orbital corrections of Landsat 5, data were acquired virtually simultaneously by multispectral scanners (MSSs) and thematic mappers (TMs) on Landsats 4 and 5. A formulation is developed for comparing the calibration of matched instruments (MSS4, MSS5 and TM4, TM5), and spectral interpolation is used to compare the calibration of the nearly equivalent shortwave channels of all four instruments. The MSS instruments are more closely matched in gain with a difference of 6-10% vs -2-14% for the TMs, while radiance comparisons show that the MSSs and TM4 agree reasonably well for a dark surface (water), while TM5 indicates generally lower radiance values in the shortwave channels...
February 1, 1989: Applied Optics
Lindsay S Garrenton, Christopher J Stefan, Michael A McMurray, Scott D Emr, Jeremy Thorner
During response of budding yeast to peptide mating pheromone, the cell becomes markedly polarized and MAPK scaffold protein Ste5 localizes to the resulting projection (shmoo tip). We demonstrated before that this recruitment is essential for sustained MAPK signaling and requires interaction of a pleckstrin homology (PH) domain in Ste5 with phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] in the plasma membrane. Using fluorescently tagged high-affinity probes specific for PtdIns(4,5)P(2), we have now found that this phosphoinositide is highly concentrated at the shmoo tip in cells responding to pheromone...
June 29, 2010: Proceedings of the National Academy of Sciences of the United States of America
Bettina Winzen, Bernd Koelsch, Christine Fischer, Andrea Kindler-Röhrborn
The identification of cancer susceptibility- and resistance-mediating genes is an essential prerequisite for prevention and early diagnosis of malignant tumors. Model organisms are helpful to identify variant alleles involved in pathways affecting individual cancer risk. BDIX and BDIV rats of both sexes are highly susceptible and resistant, respectively, to the development of N-ethyl-N-nitrosourea (ENU)-induced malignant peripheral nerve sheath tumors (MPNST), predominantly in the trigeminal nerves. Nevertheless, female (BDIV x BDIX) F(2) intercross rats have a lower MPNST incidence and a longer latency time than males...
November 2009: Mammalian Genome: Official Journal of the International Mammalian Genome Society
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