Cellular logisticsPub Date : 2017-12-19eCollection Date: 2017-01-01DOI: 10.1080/21592799.2017.1403530
Fiona Law, Christian E Rocheleau
{"title":"Vps34 and the Armus/TBC-2 Rab GAPs: Putting the brakes on the endosomal Rab5 and Rab7 GTPases.","authors":"Fiona Law, Christian E Rocheleau","doi":"10.1080/21592799.2017.1403530","DOIUrl":"https://doi.org/10.1080/21592799.2017.1403530","url":null,"abstract":"<p><p>Rab5 and Rab7 GTPases are key regulators of endosome maturation and lysosome fusion. They activate the class III phosphoinositide 3-kinase (PI3K) Vps34 to generate pools of phosphatidylinositol-3 phosphate [PI(3)P] on endosomes. Together PI(3)P and the GTP-bound Rabs coordinate the recruitment of endosomal regulators to drive early to late endosome maturation and ultimately lysosome fusion. Counterintuitively, loss of Vps34 results in enlarged endosomes, like those seen from expressing activated Rab GTPases. Two recent papers in the <i>Journal of Cell Science</i>, Jaber <i>et al.</i>, 2016 and Law, Seo <i>et al</i>., 2017, demonstrate that a function of Vps34 is to inactive the Rab5 and Rab7 GTPases via recruitment of the TBC1D2 family of Rab GTPase Activating Proteins (GAPs).</p>","PeriodicalId":72547,"journal":{"name":"Cellular logistics","volume":"7 4","pages":"e1403530"},"PeriodicalIF":0.0,"publicationDate":"2017-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21592799.2017.1403530","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35704509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cellular logisticsPub Date : 2017-11-29eCollection Date: 2017-01-01DOI: 10.1080/21592799.2017.1392400
Gopal P Sarma, Victor Faundez
{"title":"Integrative biological simulation praxis: Considerations from physics, philosophy, and data/model curation practices.","authors":"Gopal P Sarma, Victor Faundez","doi":"10.1080/21592799.2017.1392400","DOIUrl":"https://doi.org/10.1080/21592799.2017.1392400","url":null,"abstract":"<p><p>Integrative biological simulations have a varied and controversial history in the biological sciences. From computational models of organelles, cells, and simple organisms, to physiological models of tissues, organ systems, and ecosystems, a diverse array of biological systems have been the target of large-scale computational modeling efforts. Nonetheless, these research agendas have yet to prove decisively their value among the broader community of theoretical and experimental biologists. In this commentary, we examine a range of philosophical and practical issues relevant to understanding the potential of integrative simulations. We discuss the role of theory and modeling in different areas of physics and suggest that certain sub-disciplines of physics provide useful cultural analogies for imagining the future role of simulations in biological research. We examine philosophical issues related to modeling which consistently arise in discussions about integrative simulations and suggest a pragmatic viewpoint that balances a belief in philosophy with the recognition of the relative infancy of our state of philosophical understanding. Finally, we discuss community workflow and publication practices to allow research to be readily discoverable and amenable to incorporation into simulations. We argue that there are aligned incentives in widespread adoption of practices which will both advance the needs of integrative simulation efforts as well as other contemporary trends in the biological sciences, ranging from open science and data sharing to improving reproducibility.</p>","PeriodicalId":72547,"journal":{"name":"Cellular logistics","volume":"7 4","pages":"e1392400"},"PeriodicalIF":0.0,"publicationDate":"2017-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21592799.2017.1392400","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35704507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cellular logisticsPub Date : 2017-11-29eCollection Date: 2017-01-01DOI: 10.1080/21592799.2017.1392401
Luis S Mayorga, Meghna Verma, Raquel Hontecillas, Stefan Hoops, Josep Bassaganya-Riera
{"title":"Agents and networks to model the dynamic interactions of intracellular transport.","authors":"Luis S Mayorga, Meghna Verma, Raquel Hontecillas, Stefan Hoops, Josep Bassaganya-Riera","doi":"10.1080/21592799.2017.1392401","DOIUrl":"https://doi.org/10.1080/21592799.2017.1392401","url":null,"abstract":"<p><p>Cell biology is increasingly evolving to become a more formal and quantitative science. The field of intracellular transport is no exception. However, it is extremely challenging to formulate mathematical and computational models for processes that involve dynamic structures that continuously change their shape, position and composition, leading to information transfer and functional outcomes. The two major strategies employed to represent intracellular trafficking are based on \"ordinary differential equations\" and \"agent-\" based modeling. Both approaches have advantages and drawbacks. Combinations of both modeling strategies have promising characteristics to generate meaningful simulations for intracellular transport and allow the formulation of new hypotheses and provide new insights. In the near future, cell biologists will encounter and hopefully overcome the challenge of translating descriptive cartoon representations of biological systems into mathematical network models.</p>","PeriodicalId":72547,"journal":{"name":"Cellular logistics","volume":"7 4","pages":"e1392401"},"PeriodicalIF":0.0,"publicationDate":"2017-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21592799.2017.1392401","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35704508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cellular logisticsPub Date : 2017-09-29eCollection Date: 2017-01-01DOI: 10.1080/21592799.2017.1378794
Thu P Nguyen, Anderson R Frank, Jenna L Jewell
{"title":"Amino acid and small GTPase regulation of mTORC1.","authors":"Thu P Nguyen, Anderson R Frank, Jenna L Jewell","doi":"10.1080/21592799.2017.1378794","DOIUrl":"https://doi.org/10.1080/21592799.2017.1378794","url":null,"abstract":"<p><p>The mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase that belongs to the phosphatidylinositol 3-kinase-related kinase (PIKK) family. mTOR is the catalytic subunit of mTOR complex 1 (mTORC1), which integrates multiple environmental signals to control cell growth and metabolism. Nutrients, specifically amino acids, are the most potent stimuli for mTORC1 activation. Multiple studies have focused on how leucine and arginine activate mTORC1 through the Rag GTPases, with mechanistic details slowly emerging. Recently, a Rag GTPase-independent glutamine signaling pathway to mTORC1 has been identified, suggesting that mTORC1 is differentially regulated through distinct pathways by specific amino acids. In this review, we summarize our current understanding of how amino acids modulate mTORC1, and the role of other small GTPases in the regulation of mTORC1 activity.</p>","PeriodicalId":72547,"journal":{"name":"Cellular logistics","volume":"7 4","pages":"e1378794"},"PeriodicalIF":0.0,"publicationDate":"2017-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21592799.2017.1378794","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35704506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cellular logisticsPub Date : 2017-09-25eCollection Date: 2017-01-01DOI: 10.1080/21592799.2017.1382669
David E Stone, Elizabeth S Haswell, Elizabeth Sztul
{"title":"Finding your inner modeler: An NSF-sponsored workshop to introduce cell biologists to modeling/computational approaches.","authors":"David E Stone, Elizabeth S Haswell, Elizabeth Sztul","doi":"10.1080/21592799.2017.1382669","DOIUrl":"https://doi.org/10.1080/21592799.2017.1382669","url":null,"abstract":"<p><p>In classical Cell Biology, fundamental cellular processes are revealed empirically, one experiment at a time. While this approach has been enormously fruitful, our understanding of cells is far from complete. In fact, the more we know, the more keenly we perceive our ignorance of the profoundly complex and dynamic molecular systems that underlie cell structure and function. Thus, it has become apparent to many cell biologists that experimentation alone is unlikely to yield major new paradigms, and that empiricism must be combined with theory and computational approaches to yield major new discoveries. To facilitate those discoveries, three workshops will convene annually for one day in three successive summers (2017-2019) to promote the use of computational modeling by cell biologists currently unconvinced of its utility or unsure how to apply it. The first of these workshops was held at the University of Illinois, Chicago in July 2017. Organized to facilitate interactions between traditional cell biologists and computational modelers, it provided a unique educational opportunity: a primer on how cell biologists with little or no relevant experience can incorporate computational modeling into their research. Here, we report on the workshop and describe how it addressed key issues that cell biologists face when considering modeling including: (1) Is my project appropriate for modeling? (2) What kind of data do I need to model my process? (3) How do I find a modeler to help me in integrating modeling approaches into my work? And, perhaps most importantly, (4) why should I bother?</p>","PeriodicalId":72547,"journal":{"name":"Cellular logistics","volume":"7 4","pages":"e1382669"},"PeriodicalIF":0.0,"publicationDate":"2017-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21592799.2017.1382669","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35704505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cellular logisticsPub Date : 2017-08-08eCollection Date: 2017-01-01DOI: 10.1080/21592799.2017.1361499
Haruki Hasegawa, Mei Geng, Randal R Ketchem, Ling Liu, Kevin Graham, Frederick Jacobsen
{"title":"Intermolecular interactions involving an acidic patch on immunoglobulin variable domain and the γ2 constant region mediate crystalline inclusion body formation in the endoplasmic reticulum.","authors":"Haruki Hasegawa, Mei Geng, Randal R Ketchem, Ling Liu, Kevin Graham, Frederick Jacobsen","doi":"10.1080/21592799.2017.1361499","DOIUrl":"https://doi.org/10.1080/21592799.2017.1361499","url":null,"abstract":"<p><p>Full-length immunoglobulins (Igs) are widely considered difficult to crystallize because of their large size, N-linked glycosylation, and flexible hinge region. However, numerous cases of intracellular Ig crystallization are reported in plasma cell dyscrasias. What makes some Ig clones more prone to crystallize during biosynthesis as well as the biochemical and cell biological requirements for this cryptic event are poorly understood. To investigate the underlying process of intracellular Ig crystallization we searched for model IgGs that can induce crystalline inclusions during recombinant overexpression. By testing various subunit combinations through mixing and matching of individual subunit chains derived from a panel of human IgG clones, we identified one secretion competent IgG2λ that induced needle-like crystalline inclusions in transfected HEK293 cells. Ig crystallization rarely occurred at steady-state cell growth conditions but was easily induced when ER-to-Golgi transport was pharmacologically blocked. Homology modeling revealed the presence of a prominent negatively-charged patch on the variable domain surface. The patch was composed of eight aspartic acids, of which five were in the heavy chain variable region and three were in the light chain. Crystallization occurred only when the two subunits were co-transfected and the intracellular crystals co-localized with ER resident proteins. Furthermore, subtype switching from IgG2 to IgG1 and stepwise neutralization of the acidic patch independently abrogated Ig crystallization events. The evidence supported that the formation of needle-like crystalline inclusions in the ER was underscored by multivalent intermolecular interactions between the acidic patch and undefined determinants present on the γ2 subunit constant region.</p>","PeriodicalId":72547,"journal":{"name":"Cellular logistics","volume":"7 3","pages":"e1361499"},"PeriodicalIF":0.0,"publicationDate":"2017-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21592799.2017.1361499","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35442259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cellular logisticsPub Date : 2017-06-23eCollection Date: 2017-01-01DOI: 10.1080/21592799.2017.1340104
Laura E Newman, Cara R Schiavon, Rachel E Turn, Richard A Kahn
{"title":"The ARL2 GTPase regulates mitochondrial fusion from the intermembrane space.","authors":"Laura E Newman, Cara R Schiavon, Rachel E Turn, Richard A Kahn","doi":"10.1080/21592799.2017.1340104","DOIUrl":"10.1080/21592799.2017.1340104","url":null,"abstract":"<p><p>Mitochondria are essential, dynamic organelles that regularly undergo both fusion and fission in response to cellular conditions, though mechanisms of the regulation of their dynamics are incompletely understood. We provide evidence that increased activity of the small GTPase ARL2 is strongly correlated with an increase in fusion, while loss of ARL2 activity results in a decreased rate of mitochondrial fusion. Strikingly, expression of activated ARL2 can partially restore the loss of fusion resulting from deletion of either mitofusin 1 (MFN1) or mitofusin 2 (MFN2), but not deletion of both. We only observe the full effects of ARL2 on mitochondrial fusion when it is present in the intermembrane space (IMS), as constructs driven to the matrix or prevented from entering mitochondria are essentially inactive in promoting fusion. Thus, ARL2 is the first regulatory (small) GTPase shown to act inside mitochondria or in the fusion pathway. Finally, using high-resolution, structured illumination microscopy (SIM), we find that ARL2 and mitofusin immunoreactivities present as punctate staining along mitochondria that share a spatial convergence in fluorescence signals. Thus, we propose that ARL2 plays a regulatory role in mitochondrial fusion, acting from the IMS and requiring at least one of the mitofusins in their canonical role in fusion of the outer membranes.</p>","PeriodicalId":72547,"journal":{"name":"Cellular logistics","volume":"7 3","pages":"e1340104"},"PeriodicalIF":0.0,"publicationDate":"2017-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602422/pdf/kcll-07-03-1340104.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35442260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cellular logisticsPub Date : 2017-06-09eCollection Date: 2017-01-01DOI: 10.1080/21592799.2017.1335270
Addison Rains, Yorisha Bryant, Kaitlyn A Dorsett, Austin Culver, Jamal Egbaria, Austin Williams, Matt Barnes, Raeann Lamere, Austin R Rossi, Stephanie C Waldrep, Caroline Wilder, Elliot Kliossis, Melanie L Styers
{"title":"<i>Ypt4</i> and <i>lvs1</i> regulate vacuolar size and function in <i>Schizosaccharomyces pombe</i>.","authors":"Addison Rains, Yorisha Bryant, Kaitlyn A Dorsett, Austin Culver, Jamal Egbaria, Austin Williams, Matt Barnes, Raeann Lamere, Austin R Rossi, Stephanie C Waldrep, Caroline Wilder, Elliot Kliossis, Melanie L Styers","doi":"10.1080/21592799.2017.1335270","DOIUrl":"https://doi.org/10.1080/21592799.2017.1335270","url":null,"abstract":"<p><p>The yeast vacuole plays key roles in cellular stress responses. Here, we show that deletion of <i>lvs1</i>, the fission yeast homolog of the Chediak-Higashi Syndrome <i>CHS1</i>/<i>LYST</i> gene, increases vacuolar size, similar to deletion of the Rab4 homolog <i>ypt4</i>. Overexpression of lvs1-YFP rescued vacuolar size in <i>ypt4Δ</i> cells, but ypt4-YFP did not rescue <i>lvs1Δ</i>, suggesting that <i>lvs1</i> may act downstream of <i>ypt4</i>. Vacuoles were capable of hypotonic shock-induced fusion and recovery in both <i>ypt4Δ</i> and <i>lvs1Δ</i> cells, although recovery may be slightly delayed in <i>ypt4Δ</i>. Endocytic and secretory trafficking were not affected, but <i>ypt4Δ</i> and <i>lvs1Δ</i> strains were sensitive to neutral pH and CaCl<sub>2</sub>, consistent with vacuolar dysfunction. In addition to changes in vacuolar size, deletion of <i>ypt4</i> also dramatically increased cell size, similar to <i>tor1</i> mutants. These results implicate <i>ypt4</i> and <i>lvs1</i> in maintenance of vacuolar size and suggest that <i>ypt4</i> may link vacuolar homeostasis to cell cycle progression.</p>","PeriodicalId":72547,"journal":{"name":"Cellular logistics","volume":"7 3","pages":"e1335270"},"PeriodicalIF":0.0,"publicationDate":"2017-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21592799.2017.1335270","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35442258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cellular logisticsPub Date : 2017-04-11eCollection Date: 2017-01-01DOI: 10.1080/21592799.2017.1314237
Amber Ismael, David E Stone
{"title":"Yeast chemotropism: A paradigm shift in chemical gradient sensing.","authors":"Amber Ismael, David E Stone","doi":"10.1080/21592799.2017.1314237","DOIUrl":"https://doi.org/10.1080/21592799.2017.1314237","url":null,"abstract":"<p><p>The ability of cells to direct their movement and growth in response to shallow chemical gradients is essential in the life cycles of all eukaryotic organisms. The signaling mechanisms underlying directional sensing in chemotactic cells have been well studied; however, relatively little is known about how chemotropic cells interpret chemical gradients. Recent studies of chemotropism in budding and fission yeast have revealed 2 quite different mechanisms-biased wandering of the polarity complex, and differential internalization of the receptor and G protein. Each of these mechanisms has been proposed to play a key role in decoding mating pheromone gradients. Here we explore how they may work together as 2 essential components of one gradient sensing machine.</p>","PeriodicalId":72547,"journal":{"name":"Cellular logistics","volume":"7 2","pages":"e1314237"},"PeriodicalIF":0.0,"publicationDate":"2017-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21592799.2017.1314237","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35163534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}