PIP Kinases from the Cell Membrane to the Nucleus

Schramp, Mark; Hedman, Andrew C.; Li, Weimin; Tan, Xiaojun; Anderson, Richard A.

doi:10.1007/978-94-007-3012-0_2

Cited by 24 publications

(17 citation statements)

References 193 publications

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“…These kinases phosphorylate already-phosphorylated phosphatidyl inositols to form phosphatidylinositol bisphosphates. The PIPK functions have been mainly established for mice and humans, which include vesicular trafficking, membrane translocation, cell adhesion, chemotaxis, the cell cycle and DNA synthesis [116].…”

Section: Resultsmentioning

confidence: 99%

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

et al. 2014

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Background Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.Methodology/Principal FindingsThe T. rangeli haploid genome is ∼24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heat-shock proteins.Conclusions/SignificancePhylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets.

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Section: Resultsmentioning

confidence: 99%

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

et al. 2014

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“…These lipids are not only visualized within the nucleoplasm (Barlow et al, 2010; Boronenkov et al, 1998; Hammond et al, 2009) but are also metabolically distinct from membrane lipids (Follo et al, 2013; Keune et al, 2013; Lindsay et al, 2006; Rose and Frenster, 1965; Vann et al, 1997). Further, many lipid signaling and metabolic enzymes shuttle into the nucleus (Bassi et al, 2013; Boronenkov et al, 1998; Schramp et al, 2012), however it is unknown if these enzymes perform the same functions within the nucleoplasm as they perform at cytoplasmic membranes. The simplest explanation of these data is that non-membrane nuclear lipids are bound by soluble nuclear proteins, and that this association alters which enzymes can modify/metabolize them (Barlow et al, 2010; Lindsay et al, 2006).…”

Section: Nuclear Lipid Signaling and Sf-1mentioning

confidence: 99%

Disentangling biological signaling networks by dynamic coupling of signaling lipids to modifying enzymes

Blind

2014

Advances in Biological Regulation

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An unresolved problem in biological signal transduction is how particular branches of highly interconnected signaling networks can be decoupled, allowing activation of specific circuits within complex signaling architectures. Although signaling dynamics and spatiotemporal mechanisms serve critical roles, it remains unclear if these are the only ways cells achieve specificity within networks. The transcription factor Steroidogenic Factor-1 (SF-1) is an excellent model to address this question, as it forms dynamic complexes with several chemically distinct lipid species (phosphatidylinositols, phosphatidylcholines and sphingolipids). This property is important since lipids bound to SF-1 are modified by lipid signaling enzymes (IPMK & PTEN), regulating SF-1 biological activity in gene expression. Thus, a particular SF-1/lipid complex can interface with a lipid signaling enzyme only if SF-1 has been loaded with a chemically compatible lipid substrate. This mechanism permits dynamic downstream responsiveness to constant upstream input, disentangling specific pathways from the full network. The potential of this paradigm to apply generally to nuclear lipid signaling is discussed, with particular attention given to the nuclear receptor superfamily of transcription factors and their phospholipid ligands.

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“…In this manner, phosphatidylinositol 4,5-bisphosphate (PIP 2 ) on the plasma membrane plays a key role in regulating actin assembly, endocytosis, exocytosis, phagocytosis, and ion channel function (Martin, 2001; Di Paolo and De Camilli, 2006; Suh and Hille, 2008; Koch and Holt, 2012). Processes near membrane domains of PIP 2 may be regulated by local PIP 2 synthesis and degradation (Schramp et al ., 2012; Zhang et al ., 2012). The spatial and temporal regulation of PIP 2 was characterized for phagocytosis, where an initial enhanced synthesis of PIP 2 in early phagosome formation transitions to a decrease in PIP 2 , with diacylglycerol (DAG) formation during phagosome closure (Botelho et al ., 2000; Flannagan et al ., 2012).…”

Section: Introductionmentioning

confidence: 99%