1949-0992 BioArchitecture BioArchitecture Austin, Tx Landes Bioscience quarterly January/February 2011 - http://dx.doi.org/10.4161/bioa http://www.landesbioscience.com/journals/BioArchitecture/ 1949-0992 Katherine B. Szarama Ruben Stepanyan Ronald S. Petralia Nuria Gavara Gregory I. Frolenkov Matthew W. Kelley and Richard S. Chadwick BioArchitecture Fibroblast growth factor receptor 3 regulates microtubule formation and cell surface mechanical properties in the developing organ of Corti Landes Bioscience 2012-11-01 214 - 219 BioArchitecture 2-6 Landes Bioscience Fibroblast Growth Factor (Fgf) signaling is involved in the exquisite cellular patterning of the developing cochlea, and is necessary for proper hearing function. Our previous data indicate that Fgf signaling disrupts actin, which impacts the surface stiffness of sensory outer hair cells (OHCs) and non-sensory supporting pillar cells (PCs) in the organ of Corti. Here, we used Atomic Force Microscopy (AFM) to measure the impact of loss of function of Fgf-receptor 3, on cytoskeletal formation and cell surface mechanical properties. We find a 50% decrease in both OHC and PC surface stiffness, and a substantial disruption in microtubule formation in PCs. Moreover, we find no change in OHC electromotility of Fgfr3-deficient mice. To further understand the regulation by Fgf-signaling on microtubule formation, we treated wild-type cochlear explants with Fgf-receptor agonist Fgf2, or antagonist SU5402, and find that both treatments lead to a significant reduction in β-Tubulin isotypes I&II. To identify downstream transcriptional targets of Fgf-signaling, we used QPCR arrays to probe 84 cytoskeletal regulators. Of the 5 genes significantly upregulated following treatment, <em>Clasp2</em>, <em>Mapre2</em> and <em>Mark2</em> impact microtubule formation. We conclude that microtubule formation is a major downstream effector of Fgf-receptor 3, and suggest this pathway impacts the formation of fluid spaces in the organ of Corti. http://dx.doi.org/10.4161/bioa.22332 http://www.landesbioscience.com/journals/BioArchitecture/article/22332/ article Short Communication 1949-0992 Karen S. Lyle Jose A. Corleto and Torsten Wittmann BioArchitecture Microtubule dynamics regulation contributes to endothelial morphogenesis Landes Bioscience 2012-11-01 220 - 227 BioArchitecture 2-6 Landes Bioscience Because little is known how microtubules contribute to cell migration in a physiological three-dimensional environment, we analyzed microtubule function and dynamics during in vitro angiogenesis in which endothelial cells form networks on a reconstituted basement membrane. Endothelial network formation resulted from distinct cell behaviors: matrix reorganization by myosin-mediated contractile forces, and active cell migration along reorganized, bundled matrix fibers. Inhibition of microtubule dynamics inhibited persistent cell migration, but not matrix reorganization. In addition, microtubule polymerization dynamics and CLASP2-binding to microtubules were spatially regulated to promote microtubule growth into endothelial cell protrusions along matrix tension tracks. We propose that microtubules counter-act contractile forces of the cortical actin cytoskeleton and are required to stabilize endothelial cell protrusions in a soft three-dimensional environment. http://dx.doi.org/10.4161/bioa.22335 http://www.landesbioscience.com/journals/BioArchitecture/article/22335/ article Short Communication 1949-0992 Lise N. Munsie and Ray Truant BioArchitecture The role of the cofilin-actin rod stress response in neurodegenerative diseases uncovers potential new drug targets Landes Bioscience 2012-11-01 204 - 208 BioArchitecture 2-6 Landes Bioscience The cofilin-actin rod stress response is an actin cytoskeletal dynamic arrest that occurs in cells under a variety of stress conditions. Upon stress, the rapidly activated cofilin saturates actin filaments causing them to bundle into rod structures in either the nucleus or cytoplasm, halting actin polymerization and thus freeing ATP. Importantly, these rods dissociate quickly following relief of the transient stress. The rods form inappropriately in neurons involved in the progression of Alzheimer disease (AD) and we have linked dysfunctional dynamics of the nuclear rod response to Huntington disease (HD). Cofilin levels are also perturbed in Parkinson disease (PD), and profilin, an actin binding protein with opposite action to cofilin, is mutated in Amyotrophic Lateral Sclerosis (ALS). The persistence of the rods post-stress suggests that critical molecular switches to turn this response both on and off are being affected in neurodegeneration. We have recently shown that the cofilin protein is regulated by highly conserved nuclear import and export signals and that these signals are required to be functional for an appropriate rod formation during stress. The ability of cofilin to form rods is required in a cell culture model for cells to be resistant to apoptosis under stress conditions, indicating that a normal cofilin-actin rod response is likely integral to proper cell health in higher order organisms. Here we hypothesize on the potential physiological function of nuclear cofilin-actin rods and why the dysregulation of this response could lead to the selective vulnerability of the most susceptible populations of cells in HD. We further suggest that learning more about this cytoskeletal cell stress response will open up new avenues for drug target discovery in neurodegenerative disorders. http://dx.doi.org/10.4161/bioa.22549 http://www.landesbioscience.com/journals/BioArchitecture/article/22549/ article Commentary 1949-0992 Irina V. Novikova Scott P. Hennelly and Karissa Y. Sanbonmatsu BioArchitecture Sizing up long non-coding RNAs: Do lncRNAs have secondary and tertiary structure? Landes Bioscience 2012-11-01 189 - 199 BioArchitecture 2-6 Landes Bioscience Long noncoding RNAs (lncRNAs) play a key role in many important areas of epigenetics, stem cell biology, cancer, signaling and brain function. This emerging class of RNAs constitutes a large fraction of the transcriptome, with thousands of new lncRNAs reported each year. The molecular mechanisms of these RNAs are not well understood. Currently, very little structural data exist. We review the available lncRNA sequence and secondary structure data. Since almost no tertiary information is available for lncRNAs, we review crystallographic structures for other RNA systems and discuss the possibilities for lncRNAs in the context of existing constraints. http://dx.doi.org/10.4161/bioa.22592 http://www.landesbioscience.com/journals/BioArchitecture/article/22592/ article Mini-Review 1949-0992 Peter Gunning BioArchitecture BioArchitecture: The organization and regulation of biological space Landes Bioscience 2012-11-01 200 - 203 BioArchitecture 2-6 Landes Bioscience BioArchitecture is a term used to describe the organization and regulation of biological space. It applies to the principles which govern the structure of molecules, polymers and mutiprotein complexes, organelles, membranes and their organization in the cytoplasm and the nucleus. It also covers the integration of cells into their three dimensional environment at the level of cell-matrix, cell-cell interactions, integration into tissue/organ structure and function and finally into the structure of the organism. This review will highlight studies at all these levels which are providing a new way to think about the relationship between the organization of biological space and the function of biological systems. http://dx.doi.org/10.4161/bioa.22726 http://www.landesbioscience.com/journals/BioArchitecture/article/22726/ article Review 1949-0992 Scott J. Nowak and Mary K. Baylies BioArchitecture Akirin: A context-dependent link between transcription and chromatin remodeling Landes Bioscience 2012-11-01 209 - 213 BioArchitecture 2-6 Landes Bioscience Embryonic patterning relies upon an exquisitely timed program of gene regulation. While the regulation of this process via the action of transcription factor networks is well understood, new lines of study have highlighted the importance of a concurrently regulated program of chromatin remodeling during development. Chromatin remodeling refers to the manipulation of the chromatin architecture through rearrangement, repositioning, or restructuring of nucleosomes to either favor or hinder the expression of associated genes. While the role of chromatin remodeling pathways during tumor development and cancer progression are beginning to be clarified, the roles of these pathways in the course of tissue specification, morphogenesis and patterning remains relatively unknown. Further, relatively little is understood as to the mechanism whereby developmentally critical transcription factors coordinate with chromatin remodeling factors to optimize target gene loci for gene expression. Such a mechanism might involve direct transcription factor/chromatin remodeling factor interactions, or could likely be mediated via an unknown intermediary. Our group has identified the relatively unknown protein Akirin as a putative member of this latter group: a secondary cofactor that serves as an interface between a developmentally critical transcription factor and the chromatin remodeling machinery. This role for the Akirin protein suggests a novel regulatory mode for regulating gene expression during development. http://dx.doi.org/10.4161/bioa.22907 http://www.landesbioscience.com/journals/BioArchitecture/article/22907/ article Commentary