Friday, January 28, 2011

Hot off the presses! Feb 01 trends cell biol

The Feb 01 issue of the trends cell biol is now up on Pubget (About trends cell biol): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

  • Editorial Board
    - trends cell biol 21(2):i (2011)
  • Autophagy: a broad role in unconventional protein secretion?
    - trends cell biol 21(2):67-73 (2011)
    Autophagy, a cellular 'self-eating' process in eukaryotic cells, exists in both a basal and in an activated state that is induced in response to starvation. Basal and induced autophagy are associated with the packaging of cellular components, including damaged and/or redundant organelles, into double-membrane vesicles called autophagosomes, followed by autophagosome fusion with lysosomes, in which their contents are degraded and recycled. Recent results highlight a novel role for autophagy that does not involve lysosomal degradation of autophagosomal contents, but instead involves their redirection towards the extracellular delivery of an unconventionally secreted protein. Here, we discuss these findings, evaluate the strength of evidence, consider their implications for the field of protein trafficking, and suggest the next steps required to probe this interesting pathway.
  • Inactive yet indispensable: the tale of Jarid2
    - trends cell biol 21(2):74-80 (2011)
    Methylation of histone tails is believed to be important for the establishment and inheritance of gene expression programs during development. Jarid2/Jumonji is the founding member of a family of chromatin modifiers with histone demethylase activity. Although Jarid2 contains amino acid substitutions that are thought to abolish its catalytic activity, it is essential for the development of multiple organs in mice. Recent studies have shown that Jarid2 is a component of the polycomb repressive complex 2 and is required for embryonic stem (ES) cell differentiation. Here, we discuss current literature on the function of Jarid2 and hypothesize that defects resulting from Jarid2 deficiency arise from a failure to correctly prime genes in ES cells that are required for later stages in development.
  • Metastasis: tumor cells becoming MENAcing
    - trends cell biol 21(2):81-90 (2011)
    During breast cancer metastasis cells emigrate from the primary tumor to the bloodstream, and this carries them to distant sites where they infiltrate and sometimes form metastases within target organs. These cells must penetrate the dense extracellular matrix comprising the basement membrane of the mammary duct/acinus and migrate toward blood and lymphatic vessels, processes that mammary tumor cells execute primarily using epidermal growth factor (EGF)-dependent protrusive and migratory activity. Here, we focus on how the actin regulatory protein Mena affects EGF-elicited movement, invasion and metastasis. Recent findings indicate that, in invasive migratory tumor cells, Mena isoforms that endow heightened sensitivity to EGF and increased protrusive and migratory abilities are upregulated, whereas other isoforms are selectively downregulated. This change in Mena isoform expression enables tumor cells to invade in response to otherwise benign EGF stimulus levels and co! uld offer an opportunity to identify metastatic risk in patients.
  • Interaction of calcineurin with substrates and targeting proteins
    - trends cell biol 21(2):91-103 (2011)
    Calcineurin is a calcium activated protein phosphatase with a major role in calcium signaling in diverse cells and organs and clinical importance as the target of the immunosuppressive drugs cyclosporin A and tacrolimus (FK506). Cell biology studies have focused mainly on the role of calcineurin in transcriptional signaling. Calcium entry in response to extracellular stimuli results in calcineurin activation, and signal transmission from the cytosol into the nucleus through dephosphorylation and nuclear translocation of the transcription factor nuclear factor of activated T cells (NFAT). This initiates a cascade of transcriptional events involved in physiological and developmental processes. Molecular analyses of the calcineurin–NFAT interaction have been extended recently to encompass the interaction of calcineurin with other substrates, targeting proteins and regulators of calcineurin activity. These studies have increased our understanding of how this essential ca! lcium activated enzyme orchestrates intracellular events in cooperation with other signaling pathways, and have suggested a link between altered calcineurin signaling and the developmental anomalies of Down syndrome.
  • PUF proteins: repression, activation and mRNA localization
    - trends cell biol 21(2):104-112 (2011)
    The eukaryotic family of RNA-binding proteins termed PUF (Pumilio and FBF) is known for its roles in cell division, differentiation and development. The best-characterized function of PUFs is as posttranscriptional repressors. Recent studies have indicated that PUFs can also activate gene expression. Moreover, it is becoming clear that PUFs facilitate mRNA localization for spatial control of expression. Here, we review the emerging concept of PUF proteins as versatile posttranscriptional regulators. We discuss how the functions of PUFs as repressors and mRNA targeting factors could be integrated by focusing on Puf3 and Puf6 from yeast and propose a model for how the roles of Puf3 in mRNA targeting to the mitochondria and mRNA repression might promote cotranslational import into mitochondria and mitochondrial biogenesis.
  • Coordination of Golgi functions by phosphatidylinositol 4-kinases
    - trends cell biol 21(2):113-121 (2011)
    Phosphatidylinositol 4-kinases (PI4Ks) regulate vesicle-mediated export from the Golgi apparatus via phosphatidylinositol 4-phosphate (PtdIns4P) binding effector proteins that control vesicle budding reactions and regulate membrane dynamics. Evidence has emerged from the characterization of Golgi PI4K effectors that vesicle budding and lipid dynamics are tightly coupled via a regulatory network that ensures that the appropriate membrane composition is established before a transport vesicle buds from the Golgi. An important hub of this network is protein kinase D, which regulates the activity of PI4K and several PtdIns4P effectors that control sphingolipid and sterol content of Golgi membranes. Other newly identified PtdIns4P effectors include Vps74/GOLPH3, a phospholipid flippase called Drs2 and Sec2, a Rab guanine nucleotide exchange factor (GEF). These effectors orchestrate membrane transformation events facilitating vesicle formation and targeting. In this review, w! e discuss how PtdIns4P signaling is integrated with membrane biosynthetic and vesicle budding machineries to potentially coordinate these crucial functions of the Golgi apparatus.
  • EHD proteins: key conductors of endocytic transport
    - trends cell biol 21(2):122-131 (2011)
    Regulation of endocytic transport is controlled by an elaborate network of proteins. Rab GTP-binding proteins and their effectors have well-defined roles in mediating specific endocytic transport steps, but until recently less was known about the four mammalian dynamin-like C-terminal Eps15 homology domain (EHD) proteins that also regulate endocytic events. In recent years, however, great strides have been made in understanding the structure and function of these unique proteins. Indeed, a growing body of literature addresses EHD protein structure, interactions with binding partners, functions in mammalian cells, and the generation of various new model systems. Accordingly, this is now an opportune time to pause and review the function and mechanisms of action of EHD proteins, and to highlight some of the challenges and future directions for the field.

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