Abstract：
:In invertebrates, UNC-45 regulates myosin stability and functions. Vertebrates have two distinct isoforms of the protein: UNC-45B, expressed in muscle cells only, and UNC-45A, expressed in all cells and implicated in regulating both non-muscle myosin II (NMII)- and microtubule (MT)-associated functions. Here, we show that, in vitro and in human and rat cells, UNC-45A binds to the MT lattice, leading to MT bending, breakage and depolymerization. Furthermore, we show that UNC-45A destabilizes MTs independent of its C-terminal NMII-binding domain and even in the presence of the NMII inhibitor blebbistatin. These findings identified UNC-45A as a novel type of MT-severing protein with a dual non-mutually exclusive role in regulating NMII activity and MT stability. Because many human diseases, from cancer to neurodegenerative diseases, are caused by or associated with deregulation of MT stability, our findings have profound implications in the biology of MTs, as well as the biology of human diseases and possible therapeutic implications for their treatment.This article has an associated First Person interview with the joint first authors of the paper.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Habicht J,Mooneyham A,Hoshino A,Shetty M,Zhang X,Emmings E,Yang Q,Coombes C,Gardner MK,Bazzaro Mdoi
10.1242/jcs.248815subject
Has Abstractpub_date
2021-01-08 00:00:00issue
1eissn
0021-9533issn
1477-9137pii
jcs.248815journal_volume
134pub_type
杂志文章abstract：:Microtubules--polymers of tubulin--perform essential functions, including regulation of cell shape, intracellular transport and cell motility. How microtubules are adapted to perform multiple diverse functions is not well understood. Post-translational modifications of tubulin subunits diversify the outer and luminal ...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.063727
更新日期：2010-10-15 00:00:00
abstract：:The process of cell migration is initiated by protrusion at the leading edge of the cell, the formation of peripheral adhesions, the exertion of force on these adhesions, and finally the release of the adhesions at the rear of the cell. Focal adhesion kinase (FAK) is intimately involved in the regulation of this proce...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02380
更新日期：2005-06-15 00:00:00
abstract：:Circadian rhythms exist in most living organisms. The general molecular mechanisms that are used to generate 24-hour rhythms are conserved among organisms, although the details vary. These core clocks consist of multiple regulatory feedback loops, and must be coordinated and orchestrated appropriately for the fine-tun...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.065771
更新日期：2011-02-01 00:00:00
abstract：:The notion that cell shape and spreading can regulate cell proliferation has evolved over several years, but only recently has this been linked to forces from within and upon the cell. This emerging area of mechanical signaling is proving to be wide-spread and important for all cell types. The microenvironment that su...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.067009
更新日期：2011-04-15 00:00:00
abstract：:Membrane-bound transferrin-like protein (MTf), a glycosylphosphatidylinositol-anchored protein, is expressed at high levels in many tumors and in several fetal and adult tissues including cartilage and the intestine, as well as in the amyloid plaques of Alzheimer's disease, although its role remains unknown. MTf is on...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00393
更新日期：2003-05-15 00:00:00
abstract：:Apoptosis, or programmed cell death, involves a cascade of regulatory events leading to the activation of specific proteases. However, the key substrates for these proteases remain to be identified. We previously demonstrated that levels of five unidentified polypeptides were specifically increased in neurons from emb...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-03-01 00:00:00
abstract：:Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival, neurite outgrowth and synaptic plasticity by activating the receptor tropomyosin receptor kinase B (TrkB, also known as NTRK2). TrkB has been shown to undergo recycling after BDNF stimulation. We have previously reported that full-l...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.160259
更新日期：2015-03-15 00:00:00
abstract：:Basement membranes are complex extracellular matrices contributing to the regulation of growth, migration and differentiation of many cell types. However, little is known about the mechanisms regulating the deposition and assembly of basement membrane from its constituents. We have investigated the role of extracellul...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1991-06-01 00:00:00
abstract：:Ca2+ is a second messenger in many physiological and phytopathological processes. Peroxisomes are subcellular compartments with an active oxidative and nitrosative metabolism. Previous studies have demonstrated that peroxisomal nitric oxide (NO) generation is dependent on Ca2+ and calmodulin (CaM). Here, we used Arabi...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.201467
更新日期：2018-01-29 00:00:00
abstract：:Primary cilia are conserved organelles that play crucial roles as mechano- and chemosensors, as well as transducing signaling cascades. Consequently, ciliary dysfunction results in a broad range of phenotypes: the ciliopathies. Bardet-Biedl syndrome (BBS), a model ciliopathy, is caused by mutations in 16 known genes. ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.089375
更新日期：2012-01-15 00:00:00
abstract：:Blocking expression of EhCaBP1, a calmodulin-like, four EF-hand protein from the protozoan parasite Entamoeba histolytica, resulted in inhibition of cellular proliferation. In this paper we report that EhCaBP1 is involved in dynamic changes of the actin cytoskeleton. Both endocytosis and phagocytosis were severely imp...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.01198
更新日期：2004-07-15 00:00:00
abstract：:In chondrocytes, PTHrP maintains them in a proliferative state and prevents premature hypertrophy. The mechanism by which PTHrP does this is not fully understood. Both Runx2 and Runx3 are required for chondrocyte maturation. We recently demonstrated that cyclin D1 induces Runx2 protein phosphorylation and degradation....
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.040709
更新日期：2009-05-01 00:00:00
abstract：:The cross-striated muscle from the heart ventricle and the smooth penis retractor muscle of the freshwater snail Lymnaea stagnalis have been investigated by X-ray microanalysis to establish whether lanthanum can cross the plasma membrane, as has been reported by other investigators. Tissues were incubated in 1 mM ioni...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1985-04-01 00:00:00
abstract：:Evidence from various systems suggests that either asters or the midzone of the mitotic spindle are the predominant determinants of cleavage plane position. Disrupting spindle midzone formation in the one-cell Caenorhabditis elegans embryo, such as by using mutants of the centralspindlin component ZEN-4, prevents comp...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.03447
更新日期：2007-05-15 00:00:00
abstract：:Cyclic stretch is an artificial model of mechanical force loading, which induces the reorientation of vascular endothelial cells and their stress fibers in a direction perpendicular to the stretch axis. Rho family GTPases are crucial for cyclic-stretch-induced endothelial cell reorientation; however, the mechanism und...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.157503
更新日期：2015-05-01 00:00:00
abstract：:Notch signalling is used throughout the animal kingdom to spatially and temporally regulate cell fate, proliferation and differentiation. Its importance is reflected in the dramatic effects produced on both development and health by small variations in the strength of the Notch signal. The Down-syndrome-associated kin...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.044354
更新日期：2009-05-15 00:00:00
abstract：:The 16 kDa proteolipid (subunit c) of the eukaryotic vacuolar H(+)-ATPase (V-ATPase) is closely related to the ductin polypeptide that forms the connexon channel of gap junctions in the crustacean Nephrops norvegicus. Here we show that the major protein component of Manduca sexta gap junction preparations is a 16 kDa ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-07-01 00:00:00
abstract：:What forces drive chromosome segregation remains one of the most challenging questions in cell division. Even though the duration of anaphase is short, it is of utmost importance for genome fidelity that no mistakes are made. Seminal studies in model organisms have revealed different mechanisms operating during chromo...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.231985
更新日期：2019-09-16 00:00:00
abstract：:Stages of meiosis from the bluebell Endymion non-scriptus (L.) were studied by electron microscopy. The nucleolus went through the process of segregation at the beginning of meiosis with the movement to its surface of a pale-staining region. This region was shown to be the same as that called the 'L zone' or lacunae o...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1976-10-01 00:00:00
abstract：:Polarization of early embryos provides a foundation to execute essential patterning and morphogenetic events. In Caenorhabditis elegans, cell contacts polarize early embryos along their radial axis by excluding the cortical polarity protein PAR-6 from sites of cell contact, thereby restricting PAR-6 to contact-free ce...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.124594
更新日期：2013-04-01 00:00:00
abstract：:The LEM domain (for lamina-associated polypeptide, emerin, MAN1 domain) defines a group of nuclear proteins that bind chromatin through interaction of the LEM motif with the conserved DNA crosslinking protein, barrier-to-autointegration factor (BAF). Here, we describe a LEM protein annotated in databases as 'Ankyrin r...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.098392
更新日期：2012-02-15 00:00:00
abstract：:During the last phase of oogenesis in Drosophila, nurse cell cytoplasm can be seen to be streaming into the growing oocyte when visualized in time-lapse films. This process can be reversibly inhibited by cytochalasins. The distribution of F-actin filaments in the nurse cells has been studied by staining with rhodamine...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1986-02-01 00:00:00
abstract：:The effect of a synthetic peptide consisting of Arg-Gly-Asp-Ser (RGDS), the amino acid sequence representing the fibroblast attachment site in fibronectin (FN), was tested on migrating newt epidermal cells. In one approach, skin explants were placed on the bottom of plastic dishes coated with human FN, human fibrinoge...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1987-05-01 00:00:00
abstract：:CDC6, a replication licensing protein, is partially exported to the cytoplasm in human cells through phosphorylation by Cdk during S phase, but a significant proportion remains in the nucleus. We report here that human CDC6 physically interacts with ATR, a crucial checkpoint kinase, in a manner that is stimulated by p...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.058693
更新日期：2010-01-15 00:00:00
abstract：:Ligand-dependent nuclear import is crucial for the function of the androgen receptor (AR) in both health and disease. The unliganded AR is retained in the cytoplasm but, on binding 5alpha-dihydrotestosterone, it translocates into the nucleus and alters transcription of its target genes. Nuclear import of AR is mediate...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.022103
更新日期：2008-04-01 00:00:00
abstract：:Cadherins are transmembrane glycoproteins involved in Ca2+-dependent cell-cell adhesion. Using L cells expressing one of three functional E-cadherin constructs, the wild-type, a chimeric molecule with alpha-catenin (EalphaC), and a tail-less one, we determined the effect of v-Src expression on E-cadherin-mediated adhe...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-02-01 00:00:00
abstract：:Removal of the pro-domain of a cysteine protease is essential for activation of the enzyme. We have engineered a cysteine protease (CPB2.8) of the protozoan parasite Leishmania mexicana by site-directed mutagenesis to remove the active site cysteine (to produce CPB(C25G)). When CPB(C25G) was expressed in a L. mexicana...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-11-01 00:00:00
abstract：:During animal development, cells need to sense and adapt to mechanical forces from their environment. Ultimately, these forces are transduced through the actomyosin cortex. How the cortex simultaneously responds to and creates forces during cytokinesis is not well understood. Here we show that, under mechanical stress...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.231357
更新日期：2019-10-09 00:00:00
abstract：:Occludin and 18 distinct members of the claudin family are tetra-span transmembrane proteins that are localized in cell-specific tight junctions (TJs). A previous study showed that expression of chick occludin in Madin-Darby canine kidney (MDCK) cells raised transepithelial electrical resistance (TER) and, paradoxical...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-10-01 00:00:00
abstract：:The intracellular protozoan parasite Toxoplasma gondii, like all members of the phylum Apicomplexa, is known to possess many organelles: in addition to mitochondria and the compartments of the secretory pathway, there is a reduced chloroplast (the apicoplast) and the phylum-specific components of the apical complex: d...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-07-01 00:00:00
