| 1. |
- Alvarado-Kristensson, Maria, et al.
(författare)
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SADB phosphorylation of gamma-tubulin regulates centrosome duplication.
- 2009
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Ingår i: Nature Cell Biology. - : Springer Science and Business Media LLC. - 1465-7392 .- 1476-4679. ; 11:9, s. 86-1081
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Tidskriftsartikel (refereegranskat)abstract
- Symmetrical cell division requires duplication of DNA and protein content to generate two daughter cells. Centrosomes also duplicate during cell division, but the mechanism controlling this process is incompletely understood. We describe an alternative splice form of SadB encoding a short SADB Ser/Thr kinase whose activity fluctuates during the cell cycle, localizes to centrosomes, and controls centrosome duplication. Reduction of endogenous SADB levels diminished centrosome numbers, whereas enhanced SADB expression induced centrosome amplification. SADB exerted this action through phosphorylation of gamma-tubulin on Ser 131, as expression of a phosphomimetic Ser 131-to-Asp gamma-tubulin mutant alone increased centrosome numbers, whereas non-phosphorylatable Ala 131-gamma-tubulin impaired centrosome duplication. We propose that SADB kinase activity controls centrosome homeostasis by regulating phosphorylation of gamma-tubulin.
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| 2. |
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| 3. |
- Boström, Pontus, 1982, et al.
(författare)
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SNARE proteins mediate fusion between cytosolic lipid droplets and are implicated in insulin sensitivity.
- 2007
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Ingår i: Nature cell biology. - : Springer Science and Business Media LLC. - 1465-7392 .- 1476-4679. ; 9:11, s. 1286-93
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Tidskriftsartikel (refereegranskat)abstract
- The accumulation of cytosolic lipid droplets in muscle and liver cells has been linked to the development of insulin resistance and type 2 diabetes. Such droplets are formed as small structures that increase in size through fusion, a process that is dependent on intact microtubules and the motor protein dynein. Approximately 15% of all droplets are involved in fusion processes at a given time. Here, we show that lipid droplets are associated with proteins involved in fusion processes in the cell: NSF (N-ethylmaleimide-sensitive-factor), alpha-SNAP (soluble NSF attachment protein) and the SNAREs (SNAP receptors), SNAP23 (synaptosomal-associated protein of 23 kDa), syntaxin-5 and VAMP4 (vesicle-associated membrane protein 4). Knockdown of the genes for SNAP23, syntaxin-5 or VAMP4, or microinjection of a dominant-negative mutant of alpha-SNAP, decreases the rate of fusion and the size of the lipid droplets. Thus, the SNARE system seems to have an important role in lipid droplet fusion. We also show that oleic acid treatment decreases the insulin sensitivity of heart muscle cells, and this sensitivity is completely restored by transfection with SNAP23. Thus, SNAP23 might be a link between insulin sensitivity and the inflow of fatty acids to the cell.
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| 4. |
- Ikeda, Yoshihisa, et al.
(författare)
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Local auxin biosynthesis modulates gradient-directed planar polarity in Arabidopsis
- 2009
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Ingår i: Nature Cell Biology. - : Nature Publishing Group. - 1465-7392 .- 1476-4679. ; 11:6, s. 731-738
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Tidskriftsartikel (refereegranskat)abstract
- The coordination of cell polarity within the plane of a single tissue layer (planar polarity) is a crucial task during development of multicellular organisms. Mechanisms underlying establishment of planar polarity, however, differ substantially between plants and animals. In Arabidopsis thaliana, planar polarity of root-hair positioning along epidermal cells is coordinated towards maximum concentration of an auxin gradient in the root tip. This gradient has been hypothesized to be sink-driven and computational modelling suggests that auxin efflux carrier activity may be sufficient to generate the gradient in the absence of auxin biosynthesis in the root. Here, we demonstrate that the Raf-like kinase CONSTITUTIVE TRIPLE RESPONSE1 (CTR1; Refs 8, 9) acts as a concentration-dependent repressor of a biosynthesis-dependent auxin gradient that modulates planar polarity in the root tip. We analysed auxin biosynthesis and concentration gradients in a variety of root-hair-position mutants affected in CTR1 activity, auxin biosynthesis and transport. Our results reveal that planar polarity relies on influx- and efflux-carrier-mediated auxin redistribution from a local biosynthesis maximum. Thus, a local source of auxin biosynthesis contributes to gradient homeostasis during long-range coordination of cellular morphogenesis.
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| 5. |
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| 6. |
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| 7. |
- Kvist, Anders, et al.
(författare)
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Promoter usage of BRCA1-IRIS
- 2005
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Ingår i: Nature Cell Biology. - : Springer Science and Business Media LLC. - 1465-7392 .- 1476-4679. ; 7:4, s. 325-326
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 8. |
- Men, Shuzhen, et al.
(författare)
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Sterol-dependent endocytosis mediates post-cytokinetic acquisition of PIN2 auxin efflux carrier polarity
- 2008
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Ingår i: Nature Cell Biology. - : Nature Publishing Group. - 1465-7392 .- 1476-4679. ; 10:2, s. 237-244
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Tidskriftsartikel (refereegranskat)abstract
- The polarization of yeast and animal cells relies on membrane sterols for polar targeting of proteins to the plasma membrane, their polar endocytic recycling and restricted lateral diffusion1, 2, 3, 4. However, little is known about sterol function in plant-cell polarity5. Directional root growth along the gravity vector requires polar transport of the plant hormone auxin. In Arabidopsis, asymmetric plasma membrane localization of the PIN–FORMED2 (PIN2) auxin transporter directs root gravitropism6, 7, 8, 9, 10. Although the composition of membrane sterols influences gravitropism and localization of two other PIN proteins11, it remains unknown how sterols contribute mechanistically to PIN polarity. Here, we show that correct membrane sterol composition is essential for the acquisition of PIN2 polarity. Polar PIN2 localization is defective in the sterol-biosynthesis mutant cyclopropylsterol isomerase1-1 (cpi1-1) which displays altered sterol composition, PIN2 endocytosis, and root gravitropism. At the end of cytokinesis, PIN2 localizes initially to both newly formed membranes but subsequently disappears from one. By contrast, PIN2 frequently remains at both daughter membranes in endocytosis-defective cpi1-1 cells. Hence, sterol composition affects post-cytokinetic acquisition of PIN2 polarity by endocytosis, suggesting a mechanism for sterol action on establishment of asymmetric protein localization.
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| 9. |
- Nygren, Jens Martin, 1976-, et al.
(författare)
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Myeloid and lymphoid contribution to non-haematopoietic lineages through irradiation-induced heterotypic cell fusion
- 2008
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Ingår i: Nature Cell Biology. - London : Nature Publishing Group. - 1465-7392 .- 1476-4679. ; 10:5, s. 584-92
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have suggested that regeneration of non-haematopoietic cell lineages can occur through heterotypic cell fusion with haematopoietic cells of the myeloid lineage. Here we show that lymphocytes also form heterotypic-fusion hybrids with cardiomyocytes, skeletal muscle, hepatocytes and Purkinje neurons. However, through lineage fate-mapping we demonstrate that such in vivo fusion of lymphoid and myeloid blood cells does not occur to an appreciable extent in steady-state adult tissues or during normal development. Rather, fusion of blood cells with different non-haematopoietic cell types is induced by organ-specific injuries or whole-body irradiation, which has been used in previous studies to condition recipients of bone marrow transplants. Our findings demonstrate that blood cells of the lymphoid and myeloid lineages contribute to various non-haematopoietic tissues by forming rare fusion hybrids, but almost exclusively in response to injuries or inflammation.
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| 10. |
- Persson, Helena, et al.
(författare)
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The non-coding RNA of the multidrug resistance-linked vault particle encodes multiple regulatory small RNAs.
- 2009
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Ingår i: Nature Cell Biology. - : Springer Science and Business Media LLC. - 1465-7392 .- 1476-4679. ; 11:10, s. 1268-1271
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Tidskriftsartikel (refereegranskat)abstract
- Vault particles are conserved organelles implicated in multidrug resistance and intracellular transport. They contain three different proteins and non-coding vault RNAs (vRNAs). Here we show that human vRNAs produce several small RNAs (svRNAs) by mechanisms different from those in the canonical microRNA (miRNA) pathway. At least one of these svRNAs, svRNAb, associates with Argonaute proteins to guide sequence-specific cleavage and regulate gene expression similarly to miRNAs. We demonstrate that svRNAb downregulates CYP3A4, a key enzyme in drug metabolism. Our findings expand the repertoire of small regulatory RNAs and assign, for the first time, a function to vRNAs that may help explain the association between vault particles and drug resistance.
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