Cytoskeleton

Although diverse actin network architectures found inside the cell have been individually reconstituted outside of the cell, how different types of actin architectures reorganize under applied forces is not entirely understood. Recently, bottom-up reconstitution has enabled studies where dynamic and phenotypic characteristics of various actin networks can be recreated in an isolated cell-like environment. Here, by creating a giant unilamellar vesicle (GUV)-based cell model encapsulating actin networks, we investigate how actin networks rearrange in response to localized stresses applied by micropipette aspiration...

No abstract text is available yet for this article.

Cellular response to the topography of their environment, known as contact guidance, is a crucial aspect to many biological processes yet remains poorly understood. A prevailing model to describe cellular contact guidance involves the lateral confinement of focal adhesions (FA) by topography as an underlying mechanism governing how cells can respond to topographical cues. However, it is not clear how this model is consistent with the well-documented depth-dependent contact guidance responses in the literature...

The muscle is the principal tissue that is capable to transform potential energy into kinetic energy. This process is due to the transformation of chemical energy into mechanical energy to enhance the movements and all the daily activities. However, muscular tissues can be affected by some pathologies associated with genetic alterations that affect the expression of proteins. As the muscle is a highly organized structure in which most of the signaling pathways and proteins are related to one another, pathologies may overlap...

To identify proteins specific to the proximal ciliary axoneme, we used iTRAQ to compare short (~2 μm) and full-length (~11 μm) axonemes of Chlamydomonas. Known compoents of the proximal axoneme such as minor dynein heavy chains and LF5 kinase as well as the ciliary tip proteins FAP256 (CEP104) and EB1 were enriched in short axonemes whereas proteins present along the length of the axoneme were of similar abundance in both samples. The iTRAQ analysis revealed that FAP93, a protein of unknown function, and protein phosphatase 2A (PP2A) are enriched in the short axonemes...

Motile cilia play various important physiological roles in eukaryotic organisms including cell motility and fertility. Inside motile cilia, large motor-protein complexes called "ciliary dyneins" coordinate their activities and drive ciliary motility. The ciliary dyneins include the outer-arm dyneins, the double-headed inner-arm dynein (IDA f/I1), and several single-headed inner-arm dyneins (IDAs a, b, c, d, e, and g). Among these single-headed IDAs, one of the ciliary dyneins, IDA d, is of particular interest because of its unique properties and subunit composition...

Both diastolic filling and systolic pumping of the heart are dependent on the passive stiffness characteristics of various mechanical elements of myocardium. However, the specific contribution from each element, including the extracellular matrix, actin filaments, microtubules, desmin intermediate filaments, and sarcomeric titin springs, remains challenging to assess. Recently, a mouse model allowing for precise and acute cleavage of the titin springs was used to remove one mechanical element after the other from cardiac fibers and record the effect on passive stiffness...

Metastasis of breast cancer cells to distant tissue sites is responsible for the majority of deaths associated with breast cancer. Previously we have examined the role of class I myosin motor protein, myosin 1e (myo1e), in cancer metastasis using the Mouse Mammary Tumor Virus-Polyoma Middle T Antigen (MMTV-PyMT) mouse model. Mice deficient in myo1e formed tumors with a more differentiated phenotype relative to the wild-type mice and formed no detectable lung metastases. In the current study, we investigated how the absence of myo1e affects cell migration and invasion in vitro, using the highly invasive and migratory breast cancer cell line, 4T1...

In vertebrate vision, photons are detected by highly specialized sensory cilia called outer segments. Photoreceptor outer segments form by remodeling the membrane of a primary cilium into a stack of flattened disks. Intraflagellar transport (IFT) is critical to the formation of most types of eukaryotic cilia including the outer segments. This review covers the state of knowledge of the role of IFT in the formation and maintenance of outer segments and the human diseases that result from mutations in genes encoding the IFT complex and associated motors...

My journey with tau started when in 1974 for the first time I isolated neurofibrillary tangles of paired helical filaments (PHFs) from autopsied Alzheimer's disease (AD) brains and discovered that they were made up of a ~50-70 KDa protein on SDS-polyacrylamide gels. Subsequently my team discovered that this PHF protein and the microtubule-associated factor called tau were one and the same protein. However, we found that tau in neurofibrillary tangles/PHFs in AD brain was abnormally hyperphosphorylated, and unlike normal tau, which promoted the assembly of tubulin into microtubules, the AD-hyperphosphorylated tau inhibited microtubule assembly...

The microtubule-associated protein tau has gained significant attention over the last several decades primarily due to its apparent role in the pathogenesis of several diseases, most notably Alzheimer's disease. While the field has focused largely on tau's potential contributions to disease mechanisms, comparably less work has focused on normal tau physiology. Moreover, as the field has grown, some misconceptions and dogmas regarding normal tau physiology have become engrained in the traditional narrative. Here, one of the most common misconceptions regarding tau, namely its normal cellular/subcellular distribution in the CNS, is discussed...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

The growth of the ciliary axonemes mainly depends on the evolutionary conserved intraflagellar transport (IFT) machinery. However, insect spermatocytes are characterized by cilium-like regions (CLRs) that elongate in the absence of IFT. It is generally believed that the dynamics of these structures relies on the free diffusion of soluble tubulin from the cytoplasm. However, this passive process could allow the elongation of short ciliary axonemes, but it is unclear whether simple diffusion of tubulin molecules can ensure the correct assembly of elongated ciliary structures...

First identified in 1975, tau was implicated in Alzheimer's disease 10 years later. Filamentous tangle inclusions were known to be made of hyperphosphorylated tau by 1991, with similar inclusions gaining recognition for being associated with other neurodegenerative diseases. In 1998, mutations in MAPT, the gene that encodes tau, were identified as the cause of a dominantly inherited form of frontotemporal dementia with abundant filamentous tau inclusions. While this result indicated that assembly of tau into aberrant filaments is sufficient to drive neurodegeneration and dementia, most cases of tauopathy are sporadic...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Microtubules, composed of αβ-tubulin heterodimers, are crucial targets for chemotherapeutic agents and possess eight binding sites. Our previous study identified cevipabulin as the only one agent capable of simultaneously binding to two different sites (Vinblastine site and The Seventh site). Binding to The Seventh site by cevipabulin induces tubulin degradation. This study aimed to investigate whether it is binding to the Vinblastine site and The Seventh site exhibited an interactive cellular effect...

The mechanisms that ensure proper assembly, activity, and turnover of myosin II filaments are fundamental to a diverse range of cellular processes. In Caenorhabditis elegans striated muscle, thick filaments contain two myosins that are functionally distinct and spatially segregated. Using transgenic double mutants, we demonstrate that the ability of increased myosin A expression to restore muscle structure and movement in myosin B mutants requires UNC-82/NUAK kinase activity. Myosin B function appears unaffected in the kinase-impaired unc-82(e1220) mutant: the recessive antimorphic effects on early assembly of paramyosin and myosin A in this mutant are counteracted by increased myosin B expression and exacerbated by loss of myosin B...

Tau was originally identified as a microtubule associated protein, and subsequently recognized to constitute the fibrillar assemblies found in Alzheimer disease and related neurodegenerative tauopathies. Point mutations in the microtubule associated protein tau (MAPT) gene cause dominantly inherited tauopathies, and most predispose it to aggregate. This indicates tau aggregation underlies pathogenesis of tauopathies. Our work has suggested that tau functions as a prion, forming unique intracellular pathological assemblies that subsequently move to other cells, inducing further aggregation that underlies disease progression...