Mystery at the heart of life

_{Denyse O'Leary

December 21, 2014

Cell biology, Intelligent Design, News}

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By Biologic Institute’s Ann Gauger, at Christianity Today’s Behemoth, the secret life of cells:

Our bodies are made up of some 100 trillion cells. We tend to think of cells as static, because that’s how they were presented to us in textbooks. In fact, the cell is like the most antic, madcap, crowded (yet fantastically efficient) city you can picture. And at its heart lies a mystery—or I should say, several mysteries—involving three special kinds of molecules: DNA, RNA, and proteins.

These molecules are assembled into long chains called polymers, and are uniquely suited for the roles they play. More importantly, life absolutely depends upon them. We have to have DNA, RNA, and protein all present and active at the same time for a living organism to live.

How they work together so optimally and efficiently is not merely amazing, but also a great enigma, a mystery that lies at the heart of life itself. More. Paywall soon after. May be worth it.

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Comments

#3409 error: Obviously it's "Why?" not "wy?"Dionisio_{May 18, 2017
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Cytokinetic abscission, the terminal step of cell division, crucially depends on the local constriction of ESCRT-III helices after cytoskeleton disassembly. While the microtubules of the intercellular bridge are cut by the ESCRT-associated enzyme Spastin, the mechanism that clears F-actin at the abscission site is unknown. Our work reveals an unexpected role for oxidoreduction in triggering local actin depolymerization to control a fundamental step of cell division.
Oxidation of F-actin controls the terminal steps of cytokinesis Stéphane Frémont, Hussein Hammich, Jian Bai, Hugo Wioland, Kerstin Klinkert, Murielle Rocancourt, Carlos Kikuti, David Stroebel, Guillaume Romet-Lemonne, Olena Pylypenko, Anne Houdusse & Arnaud Echard Nature Communications 8, Article number: 14528 doi:10.1038/ncomms14528

Did somebody say "unexpected"? Wy? Did they expect something else or nothing at all? Complex complexity.Dionisio_{May 18, 2017
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[...] the MEN pathway must act through a so far unidentified target to influence meiotic plaque formation.
The mitotic exit network [MEN] regulates spindle pole body selection during sporulation of Saccharomyces cerevisiae (MEN role in meiotic SPB inheritance) Christian Renicke, Ann-Katrin Allmann, Anne Pia Lutz, Thomas Heimerl and Christof Taxis Genetics Volume 206 Issue 1 DOI: 10.1534/genetics.116.194522

Work in progress... stay tuned. Complex complexity.Dionisio_{May 17, 2017
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We cannot fully explain the phenotypic differences of the two mutants.
The mitotic exit network [MEN] regulates spindle pole body selection during sporulation of Saccharomyces cerevisiae (MEN role in meiotic SPB inheritance) Christian Renicke, Ann-Katrin Allmann, Anne Pia Lutz, Thomas Heimerl and Christof Taxis Genetics Volume 206 Issue 1 DOI: 10.1534/genetics.116.194522

Is there anything they can fully explain? Complex complexity.Dionisio_{May 17, 2017
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Surprisingly, we found a positive effect of Nud1 depletion on spore numbers conversely to that of the nud1-2 allele (Gordon et al. 2006), pointing to an inhibitory function of Nud1 on MP formation.
The mitotic exit network [MEN] regulates spindle pole body selection during sporulation of Saccharomyces cerevisiae (MEN role in meiotic SPB inheritance) Christian Renicke, Ann-Katrin Allmann, Anne Pia Lutz, Thomas Heimerl and Christof Taxis Genetics Volume 206 Issue 1 DOI: 10.1534/genetics.116.194522

Did somebody say “Surprisingly”? Why? (see comment @3401) Complex complexity.Dionisio_{May 17, 2017
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An interesting[*] question is the intrinsic activation mechanism of the MEN. The high conservation of Hippo signaling provokes[**] the question if a similar activation mechanism is in place in budding yeast meiosis.
The mitotic exit network [MEN] regulates spindle pole body selection during sporulation of Saccharomyces cerevisiae (MEN role in meiotic SPB inheritance) Christian Renicke, Ann-Katrin Allmann, Anne Pia Lutz, Thomas Heimerl and Christof Taxis Genetics Volume 206 Issue 1 DOI: 10.1534/genetics.116.194522

(*) there are many interesting questions in Biology (**) many things in Biology provoke questions Complex complexity.Dionisio_{May 17, 2017
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Surprisingly, Mob1? or Dbf2? Dbf20? mutants had a much weaker sporulation defect than the triple mutant. Thus, the coactivator Mob1 and/or the kinases Dbf2/20 might form sporulation-specific complexes with yet unknown binding partners.
The mitotic exit network [MEN] regulates spindle pole body selection during sporulation of Saccharomyces cerevisiae (MEN role in meiotic SPB inheritance) Christian Renicke, Ann-Katrin Allmann, Anne Pia Lutz, Thomas Heimerl and Christof Taxis Genetics Volume 206 Issue 1 DOI: 10.1534/genetics.116.194522

Did somebody say "Surprisingly"? Why? (see comment @3401) Complex complexity.Dionisio_{May 17, 2017
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In mitosis, the MEN is required for establishment of spindle polarity [...] During the developmental program of sporulation, a rewiring of the MEN takes place.
The mitotic exit network [MEN] regulates spindle pole body selection during sporulation of Saccharomyces cerevisiae (MEN role in meiotic SPB inheritance) Christian Renicke, Ann-Katrin Allmann, Anne Pia Lutz, Thomas Heimerl and Christof Taxis Genetics Volume 206 Issue 1 DOI: 10.1534/genetics.116.194522

Did somebody say "rewiring"? Complex complexity.Dionisio_{May 17, 2017
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The decision how many and which SPBs and their associated genomes will be incorporated into spores takes place at the onset of meiosis II by formation of meiotic plaques at selected SPBs [...]
The mitotic exit network [MEN] regulates spindle pole body selection during sporulation of Saccharomyces cerevisiae (MEN role in meiotic SPB inheritance) Christian Renicke, Ann-Katrin Allmann, Anne Pia Lutz, Thomas Heimerl and Christof Taxis Genetics Volume 206 Issue 1 DOI: 10.1534/genetics.116.194522

Did somebody say "decision"? Who decides? Complex complexity.Dionisio_{May 17, 2017
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***** --- oOo --- ***** The words "surprisingly", "unexpectedly", "strikingly" sometimes could be justified because they may point to a flaw in the experiment or to a mistake in its sequence of steps. However, we could assume that by the time the paper was printed out it had gone through a number of reviews that could have detected any mistakes in the experiment. That's why it's valid to ask about the reasons for those words to be used. ***** --- oOo --- *****Dionisio_{May 17, 2017
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Surprisingly, in contrast to the nud1-2 allele, depletion of Nud1 induced higher spore numbers per ascus accompanied by a modest increase of unsporulated cells, whereas the sporulation efficiency was not significantly increased [...]
The mitotic exit network regulates spindle pole body selection during sporulation of Saccharomyces cerevisiae (MEN role in meiotic SPB inheritance) Christian Renicke, Ann-Katrin Allmann, Anne Pia Lutz, Thomas Heimerl and Christof Taxis Genetics Volume 206 Issue 1 DOI: 10.1534/genetics.116.194522

Did somebody say "Surprisingly"? Why? Did they expect something else or nothing at all? :) Complex complexity.Dionisio_{May 17, 2017
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How meiotic cells discriminate between the different SPBs and generate a signal for MP formation is still an open question. [...] MP grows rapidly due to a positive feedback mechanism until saturation is reached.
The mitotic exit network regulates spindle pole body selection during sporulation of Saccharomyces cerevisiae (MEN role in meiotic SPB inheritance) Christian Renicke, Ann-Katrin Allmann, Anne Pia Lutz, Thomas Heimerl and Christof Taxis Genetics Volume 206 Issue 1 DOI: 10.1534/genetics.116.194522

Complex complexity.Dionisio_{May 17, 2017
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Differential inheritance of centrosomes or corresponding structures can be observed in many organisms ranging from simple, unicellular fungi to mammals [...] During gametogenesis of S. cerevisiae, which is called sporulation, the situation is even more complex due to the higher number of genomes that must be faithfully distributed. In this developmental program, spore formation is coupled to meiotic divisions resulting in the formation of four haploid genomes encapsulated by spore walls and contained within the remnants of the former mother cell, then called an ascus [...]
The mitotic exit network regulates spindle pole body selection during sporulation of Saccharomyces cerevisiae Christian Renicke, Ann-Katrin Allmann, Anne Pia Lutz, Thomas Heimerl and Christof Taxis Genetics Volume 206 Issue 1 DOI: 10.1534/genetics.116.194522

Did somebody say "program"? Complex complexity.Dionisio_{May 16, 2017
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The budding yeast Polo-like kinase Cdc5 regulates multiple mitotic events including mitotic entry, chromosome segregation, mitotic exit, and cytokinesis [...] Whether Bfa1 retains Cdc5 at the dSPB in late anaphase to promote cytokinesis will be an interesting future study. Studying the roles of Cdc5 at each of its SPB populations will be important to explain the timing of the functions of this very complex protein during the cell cycle.
The budding yeast Polo-like kinase localizes to distinct populations at centrosomes during mitosis Vladimir V. Botchkarev Jr., Mikael V. Garabedian, Brenda Lemos, Eric Paulissen, and James E. Haber DOI: 10.1091/mbc.E16-05-0324 Molecular biology of the cell

Complex complexity.Dionisio_{May 16, 2017
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Depending on their assembly state, septin-based structures provide dynamic platforms from which the action of a significant number of protein kinases can be directed both spatially and temporally. [...] these kinases also regulate septin structure and organization, establishing an extremely complex feedback system which is yet to be fully understood. [...] there are still many mechanistic aspects of the control of septin-associated protein kinases that remain to be delineated. [...] this area of cell biology and biochemistry remains a fertile area for exploring the role of cellular structures in regulating signaling enzymes, and vice versa.
Septin-Associated Protein Kinases in the Yeast Saccharomyces cerevisiae Adam M.Perez, Gregory C. Finnigan, Françoise M. Roelants and Jeremy Thorner Front. Cell Dev. Biol. Emerging Functions of Septins DOI: 10.3389/fcell.2016.00119

Work in progress... stay tuned. Complex complexity.Dionisio_{May 16, 2017
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The actions of several septin-associated protein kinases also seem to regulate septin organization. Perhaps phosphorylation of Shs1 by Cdks and Gin4 is redundant with additional mechanisms that regulate septin assembly, but the precise consequence of these phosphorylation events on septin structure and/or function remains unclear.
Septin-Associated Protein Kinases in the Yeast Saccharomyces cerevisiae Adam M.Perez, Gregory C. Finnigan, Françoise M. Roelants and Jeremy Thorner Front. Cell Dev. Biol. Emerging Functions of Septins DOI: 10.3389/fcell.2016.00119

Complex complexity.Dionisio_{May 16, 2017
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The mechanisms responsible for the cell cycle-coupled ejection of Gin4 and the recruitment of Fpk1 are not known [...] [...] by the spatio-temporal control that Gin4 exerts on Fpk1 activity, it is clear that the septins at the bud neck are critical for protein kinase-mediated regulation of localized PM remodeling.
Septin-Associated Protein Kinases in the Yeast Saccharomyces cerevisiae Adam M.Perez, Gregory C. Finnigan, Françoise M. Roelants and Jeremy Thorner Front. Cell Dev. Biol. Emerging Functions of Septins DOI: 10.3389/fcell.2016.00119

Complex complexity.Dionisio_{May 16, 2017
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The dynamic relocation of the protein kinases of the MEN cascade to the split septin collar provides an elegant solution to help ensure that cell division only occurs after successful chromosome segregation. However, the mechanisms that promote recruitment of these kinases to the septins are unknown. Moreover, the SPOC protein kinase Kin4 also localizes to the septin rings late in anaphase, yet its function at the bud neck is not understood.
Septin-Associated Protein Kinases in the Yeast Saccharomyces cerevisiae Adam M.Perez, Gregory C. Finnigan, Françoise M. Roelants and Jeremy Thorner Front. Cell Dev. Biol. Emerging Functions of Septins DOI: 10.3389/fcell.2016.00119

Did somebody say "elegant solution"? Complex complexity.Dionisio_{May 16, 2017
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[...] the protein target (s) at each location that carry the phospho-epitopes to which the polo boxes bind have not been well defined. [...] the septin collar is the passageway through which any and all components segregated between a mother and daughter cell must pass and, hence, is a cellular structure ideally situated to monitor such cell cycle events.
Septin-Associated Protein Kinases in the Yeast Saccharomyces cerevisiae Adam M.Perez, Gregory C. Finnigan, Françoise M. Roelants and Jeremy Thorner Front. Cell Dev. Biol. Emerging Functions of Septins DOI: 10.3389/fcell.2016.00119

Complex complexity.Dionisio_{May 16, 2017
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[...] we highlight key regulatory pathways that use the septin cytoskeleton as a signaling platform to direct other orchestrated events required for successful passage through the cell cycle.
Septin-Associated Protein Kinases in the Yeast Saccharomyces cerevisiae Adam M.Perez, Gregory C. Finnigan, Françoise M. Roelants and Jeremy Thorner Front. Cell Dev. Biol. Emerging Functions of Septins DOI: 10.3389/fcell.2016.00119

Did somebody say "orchestrated"? Complex complexity.Dionisio_{May 16, 2017
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Hsl7 is a substrate of Hsl1 (Cid et al., 2001), and Hsl1 is also extensively autophosphorylated (Barral et al., 1999), but the functional consequences of these modifications remain to be determined.
Septin-Associated Protein Kinases in the Yeast Saccharomyces cerevisiae Adam M.Perez, Gregory C. Finnigan, Françoise M. Roelants and Jeremy Thorner Front. Cell Dev. Biol. Emerging Functions of Septins DOI: 10.3389/fcell.2016.00119

Complex complexity.Dionisio_{May 16, 2017
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[...] it is still not completely clear how many of these enzymes contribute directly to installing post-translational modifications on septins and/or septin-associated proteins that drive the observed dynamic changes in septin structure during cell cycle progression and how many of these enzymes are recruited to septin structures as “readers” of the status of septin assembly to phosphorylate other substrates and thereby drive subsequent downstream events.
Septin-Associated Protein Kinases in the Yeast Saccharomyces cerevisiae Adam M.Perez, Gregory C. Finnigan, Françoise M. Roelants and Jeremy Thorner Front. Cell Dev. Biol. Emerging Functions of Septins DOI: 10.3389/fcell.2016.00119

Complex complexity.Dionisio_{May 16, 2017
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Virtually all recognized checkpoint mechanisms involve regulation by reversible protein phosphorylation mediated by protein kinases and phosphoprotein phosphatases [...]
Septin-Associated Protein Kinases in the Yeast Saccharomyces cerevisiae Adam M.Perez, Gregory C. Finnigan, Françoise M. Roelants and Jeremy Thorner Front. Cell Dev. Biol. Emerging Functions of Septins DOI: 10.3389/fcell.2016.00119

Complex complexity.Dionisio_{May 16, 2017
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Septins are a family of eukaryotic GTP-binding proteins that associate into linear rods, which, in turn, polymerize end-on-end into filaments, and further assemble into other, more elaborate super-structures at discrete subcellular locations. Hence, septin-based ensembles are considered elements of the cytoskeleton. [...] septin structures represent a regulatory node at the intersection of many signaling pathways. In addition, and importantly, the activities of certain septin-associated protein kinases also regulate the state of organization of the septins themselves, creating a complex feedback loop.
Septin-Associated Protein Kinases in the Yeast Saccharomyces cerevisiae Adam M.Perez, Gregory C. Finnigan, Françoise M. Roelants and Jeremy Thorner Front. Cell Dev. Biol. Emerging Functions of Septins DOI: 10.3389/fcell.2016.00119

Complex complexity.Dionisio_{May 16, 2017
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[...] the molecular mechanism of competition between tropomyosins and ?-actinin for actin filament binding needs to be elucidated. Tropomyosins are well-established regulators of myosin II activity in muscle sarcomeres. [...] actin filaments decorated by different tropomyosin isoforms display distinct functional properties. [...] filament severing by ADF/cofilins is greatly enhanced by their co-factors, including coronin, and Aip1 in cells [35], adding more complexity to the system. The molecular mechanism underlying tropomyosin isoform segregation along actin filaments remains to be elucidated. [...] tropomyosins decorate the two structurally identical grooves along an actin filament, and thus their segregation cannot be solely determined by head-to-tail associations (i.e., some coordination must exist between the two tropomyosin-binding grooves when filament segments decorated by only one tropomyosin isoform exist). [...] the mechanisms by which different tropomyosin isoforms are targeted to their specific cellular destinations remain to be elucidated. [...] these formins may provide the link between actin filament nucleation and incorporation of specific tropomyosin isoforms into the different regions of the stress fiber network.
Tropomyosin Isoforms Specify Functionally Distinct Actin Filament Populations In Vitro. Gateva G, Kremneva E, Reindl T, Kotila T, Kogan K, Gressin L, Gunning PW, Manstein DJ, Michelot A, Lappalainen P Curr Biol. 27(5):705-713. doi: 10.1016/j.cub.2017.01.018.

Work in progress… stay tuned. Complex complexity.Dionisio_{May 15, 2017
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Actin filaments assemble into a variety of networks to provide force for diverse cellular processes [...] Tropomyosins are coiled-coil dimers that form head-to-tail polymers along actin filaments and regulate interactions of other proteins [...] [...] tropomyosin isoforms segregate to different actin filaments and specify functional properties of distinct actin filament populations.
Tropomyosin Isoforms Specify Functionally Distinct Actin Filament Populations In Vitro. Gateva G, Kremneva E, Reindl T, Kotila T, Kogan K, Gressin L, Gunning PW, Manstein DJ, Michelot A, Lappalainen P Curr Biol. 27(5):705-713. doi: 10.1016/j.cub.2017.01.018.

Complex complexity.Dionisio_{May 15, 2017
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The septins are a conserved family of GTP-binding proteins present in all eukaryotic cells except plants. The septins are regulators of spatial compartmentalization in yeast and act as key players in cytokinesis. Structure determination, the evaluation of the role of posttranslational modifications of the septins and the uncovering of so far unknown septin related processes in the living cell will represent the challenges for septin biologists for the next decade.
Septin Organization and Functions in Budding Yeast Oliver Glomb and Thomas Gronemeyer Front Cell Dev Biol. 4: 123. doi: 10.3389/fcell.2016.00123

Work in progress... stay tuned. Complex complexity.Dionisio_{May 15, 2017
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Cytokinesis is essential for the survival of all organisms. It requires concerted functions of cell signaling, force production, exocytosis, and extracellular matrix remodeling. Due to the conservation in core components and mechanisms between fungal and animal cells, the budding yeast Saccharomyces cerevisiae has served as an attractive model for studying this fundamental process.
Mechanics and regulation of cytokinesis in budding yeast Yogini P. Bhavsar-Jog, Erfei Bi DOI: 10.1016/j.semcdb.2016.12.010 Seminars in Cell and Developmental Biology

Complex complexity.Dionisio_{May 15, 2017
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Understanding the mechanisms that allow some cells but not others to escape the SPoC-mediated anaphase arrest will be an important next step in understanding the MEN and checkpoint control of the cell cycle.
LTE1 promotes exit from mitosis by multiple mechanisms Jill E. Falk, Ian W. Campbell, Kelsey Joyce, Jenna Whalen, Anupama Seshan, and Angelika Amon Mol Biol Cell. 27(25): 3991–4001. doi: 10.1091/mbc.E16-08-0563

Work in progress... stay tuned. Complex complexity.Dionisio_{May 15, 2017
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Another potential example of a situation where what seems like a bug could turn out a practical feature --using software development jargon.
This observation could have been dismissed as a leakiness of the SPoC, that is, as being the result of suboptimal regulatory mechanisms. However, the observation that the checkpoint arrest is irreversible in FEAR network mutants raises the possibility that there is perhaps purpose to this leakiness.
LTE1 promotes exit from mitosis by multiple mechanisms Jill E. Falk, Ian W. Campbell, Kelsey Joyce, Jenna Whalen, Anupama Seshan, and Angelika Amon Mol Biol Cell. 27(25): 3991–4001. doi: 10.1091/mbc.E16-08-0563

Complex complexity.Dionisio_{May 15, 2017
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