Table of Contents

Volume 2, Issue 1

  January/February 2012

Please note this issue is still accepting manuscripts.

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EDITOR'S CORNER

Open Access Article

BioArchitecture: A reflection on 2011 and looking forward to 2012

Peter Gunning
Abstract | Full Text

Volume 1 has defined the scope of BioArchitecture. From the outset we have strived to ensure that BioArchitecture is not limited to the three major polymer systems of the cytoplasm. I am happy to say that a cursory glance at the contents of volume 1 makes it clear that we are interested in all aspects of BioArchitecture from molecules to polymers to cells to tissue to the organism.




SHORT COMMUNICATION

Open Access Article

A novel role for the cytoskeletal linker protein dystonin in the maintenance of microtubule stability and the regulation of ER-Golgi transport

Scott D. Ryan, Andrew Ferrier and Rashmi Kothary
Abstract | Full Text | PDF

Crosslinking proteins maintain organelle structure and facilitate their function through the crosslinking of cytoskeletal elements. We recently found an interaction between the giant crosslinking protein dystonin-a2 and the microtubule-associated protein-1B (MAP1B), occurring in the centrosomal region of the cell. In addition, we showed that this interaction is necessary to maintain microtubule acetylation. Loss of dystonin-a2 disrupts MT stability, Golgi organization, and flux through the secretory pathway. This, coupled to our recent finding that dystonin-a2 is critical in maintaining endoplasmic reticulum (ER) structure and function, provides novel insight into the importance of dystonin in maintenance of organelle structure and in facilitating intracellular transport. These results highlight the importance of cytoskeletal dynamics in communicating signals between organelle membranes and the cytoskeleton. Importantly, they demonstrate how defects in cytoskeletal dynamics can translate into a failure of vesicular trafficking associated with neurodegenerative disease.




COMMENTARIES

Open Access Article

Nucleosome assembly and genome integrity: The fork is the link

Félix Prado and Marta Clemente-Ruiz
Abstract | Full Text

Maintaining the stability of the replication forks is one of the main tasks of the DNA damage response. Specifically, checkpoint mechanisms detect stressed forks and prevent their collapse. In the published report reviewed here we have shown that defective chromatin assembly in cells lacking either H3K56 acetylation or the chromatin assembly factors CAF1 and Rtt106 affects the integrity of advancing replication forks, despite the presence of functional checkpoints. This loss of replication intermediates is exacerbated in the absence of Rad52, suggesting that collapsed forks are rescued by homologous recombination and providing an explanation for the accumulation of recombinogenic DNA damage displayed by these mutants. These phenotypes mimic those obtained by a partial reduction in the pool of available histones and are consistent with a model in which defective histone deposition uncouples DNA synthesis and nucleosome assembly, thus making the fork more susceptible to collapse. Here, we review these findings and discuss the possibility that defects in the lagging strand represent a major source of fork instability in chromatin assembly mutants.

Open Access Article

Releasing the brakes while hanging on: Cortactin effects on actin-driven motility

Nir S. Gov and Anne Bernheim-Groswasser
Abstract | Full Text | PDF

Actin polymerization plays a major role in many cellular processes, including cell motility, vesicle trafficking, and pathogen propulsion. The transformation of the (protrusive) polymerization forces into directed motion requires that the growing filaments are positioned next to the surface. This is achieved by localization of surface actin nucleators (WASP), which then activate Arp2/3 complex to form new actin branches. Yet, the same surface-bound WASP molecule which initiates the nucleation of new actin branches, also inherently prevents the translation of the polymerization forces into motion, essentially because the WASP molecule has to be in contact with the network during the formation of the new branch. In our recent paper we show that cortactin relaxes this internal inhibition by enhancing the release of WASP-VCA molecule from the new branching site after nucleation is initiated. We show that this enhanced release has two major effects; it increases the turnover rate of branching per WASP molecule, and it decreases the friction-like force caused by the binding of the moving surface with respect to the growing actin network.

Open Access Article

Signaling network from GPCR to the actin cytoskeleton during chemotaxis

Jianshe Yan and Tian Jin
Abstract | Full Text | PDF

Chemotaxis is crucial for many physiological processes including the recruitment of leukocytes to sites of infection, trafficking of lymphocytes in the human body, and metastasis of cancer cells. A family of small proteins, chemokines, serves as the signals, and a family of G-protein coupled receptors (GPCRs) detects chemokines and direct cell migration. One of the basic questions in chemotaxis of eukaryotes is how a GPCR transduces signals to control the assembly of the actin network that generates directional force for cell migration. Over the past decade, a variety of signaling components have been implicated to transduce the GPCR signaling to the actin cytoskeleton. Studies in a lower eukaryotic organism, Dictyostelium discoideum, have allowed us to discover evolutionary conversed components involved in the GPCR-controlled actin network during chemotaxis. However, complete pathways linking GPCR to the actin network are still far from clear. Here we first summarize the previous studies on these components, and then update with our finding showing a new pathway, consisting of a GPCR, Gβγ, Elmo/Dock, Rac and Arp2/3 and actin. We suggest that this pathway serves as a direct linkage between the GPCR/G-protein, the chemoattractant sensing machinery, and the actin cytoskeleton, the machinery of cell movement during chemotaxis of eukaryotic cells.

Open Access Article

STARD9/Kif16a is a novel mitotic kinesin and antimitotic target

Jorge Z. Torres
Abstract | Full Text | PDF

Proper cell division requires the formation of the microtubule-based mitotic spindle, which mediates the dynamic movement and alignment of chromosomes to the metaphase plate and their equal transmission to daughter cells. Kinesins are molecular motors that utilize ATP hydrolysis to perform their functions and are instrumental in spindle assembly and function. Of the over 45 kinesins encoded in the human genome, only two are specifically enriched at the centrioles, Kif24 at the mother centriole and STARD9/Kif16a at the daughter centriole. While Kif24 possesses centriolar microtubule-depolymerizing activity and has been implicated in regulating cilia formation, our recent study implicates STARD9 in maintaining pericentriolar material (PCM) cohesion during early mitosis. However, very little is known about how STARD9 performs its function, including the mechanisms that recruit or retain STARD9 at the centrioles and how it cooperates with centrosome components to regulate PCM stability. Additionally, the signals leading to apoptosis in the absence of STARD9 remain to be explored.

Open Access Article

The architecture of the BubR1 tetratricopeptide tandem repeat defines a protein motif underlying mitotic checkpoint-kinetochore communication

Victor M. Bolanos-Garcia, Jakob Nilsson and Tom L. Blundell
Abstract | Full Text | PDF

The accurate and timely transmission of the genetic material to progeny during successive rounds of cell division is sine qua non for the maintenance of genome stability. Eukaryotic cells have evolved a surveillance mechanism, the mitotic spindle assembly checkpoint (SAC), to prevent premature advance to anaphase before every chromosome is properly attached to microtubules of the mitotic spindle. The architecture of the KNL1-BubR1 complex reveals important features of the molecular recognition between SAC components and the kinetochore. The interaction is important for a functional SAC as substitution of BubR1 residues engaged in KNL1 binding impaired the SAC and BubR1 recruitment into checkpoint complexes in stable cell lines. Here we discuss the implications of the disorder-to-order transition of KNL1 upon BubR1 binding for SAC signaling and propose a mechanistic model of how BUBs binding may affect the recognition of KNL1 by its other interacting partners.