Search results for "MICROTUBULES"
showing 10 items of 71 documents
Studies on the subcellular pathophysiology of sublethal chronic cell injury.
1974
Summary This paper summarizes some of the important subcellular events occurring after chronic sublethal cell injury. Chronic cell injury is defined as the result of injurious stimuli which permit cell survival though in altered steady states for protracted periods of time. The importance of ultrastructural and biochemical studies of these phenomena is emphasized. Among the phenomena discussed are alterations in lysosomes, cellular hypertrophy, fatty metamorphosis, alterations in microfilaments and microtubules, alterations in mechanisms of transcription and replication, disturbances in the cell surface and transport across the cell membrane, and alterations in intracellular transport.
The New Microtubule-Targeting Agent SIX2G Induces Immunogenic Cell Death in Multiple Myeloma
2022
Microtubule-targeting agents (MTAs) are effective drugs for cancer treatment. A novel diaryl [1,2]oxazole class of compounds binding the colchicine site was synthesized as cis-restricted-combretastatin-A-4-analogue and then chemically modified to have improved solubility and a wider therapeutic index as compared to vinca alkaloids and taxanes. On these bases, a new class of tricyclic compounds, containing the [1,2]oxazole ring and an isoindole moiety, has been synthetized, among which SIX2G emerged as improved MTA. Several findings highlighted the ability of some chemotherapeutics to induce immunogenic cell death (ICD), which is defined by the cell surface translocation of Calreticulin (CAL…
Experimental virus evolution reveals a role of plant microtubule dynamics and TORTIFOLIA1/SPIRAL2 in RNA trafficking.
2014
1 tabla y 2 figuras
Septins 2, 7 and 9 and MAP4 colocalize along the axoneme in the primary cilium and control ciliary length
2013
International audience; Septins are a large, evolutionarily conserved family of GTPases that form hetero-oligomers and interact with the actin-based cytoskeleton and microtubules. They are involved in scaffolding functions, and form diffusion barriers in budding yeast, the sperm flagellum and the base of primary cilia of kidney epithelial cells. We investigated the role of septins in the primary cilium of retinal pigmented epithelial (RPE) cells, and found that SEPT2 forms a 1:1:1 complex with SEPT7 and SEPT9 and that the three members of this complex colocalize along the length of the axoneme. Similar to observations in kidney epithelial cells, depletion of cilium-localized septins by siRN…
A novel function of Huntingtin in the cilium and retinal ciliopathy in Huntington's disease mice
2015
Huntington's disease (HD) is a neurodegenerative disorder caused by the toxic expansion of polyglutamine in the Huntingtin (HTT) protein. The pathomechanism is complex and not fully understood. Increasing evidence indicates that the loss of normal protein function also contributes to the pathogenesis, pointing out the importance of understanding the physiological roles of HTT. We provide evidence for a novel function of HTT in the cilium. HTT localizes in diverse types of cilia — including 9 + 0 non-motile sensory cilia of neurons and 9 + 2 motile multicilia of trachea and ependymal cells — which exert various functions during tissue development and homeostasis. In the photoreceptor cilium,…
Shortstop Recruits EB1/APC1 and Promotes Microtubule Assembly at the Muscle-Tendon Junction
2003
Abstract Background: Shot (previously named Kakapo), is a Drosophila Plakin family member containing both Actin binding and microtubule binding domains. In Drosophila , it is required for a wide range of processes, including axon extension, dendrite formation, axonal terminal arborization at the neuromuscular junction, tendon cell development, and adhesion of wing epithelium. Results: To address how Shot exerts its activity at the molecular level, we investigated the molecular interactions of Shot with candidate proteins in mature larval tendon cells. We show that Shot colocalizes with EB1/APC1 and with a compact microtubule array extending between the muscle-tendon junction and the cuticle…
Stabilizing versus Destabilizing the Microtubules: A Double-Edge Sword for an Effective Cancer Treatment Option?
2015
Microtubules are dynamic and structural cellular components involved in several cell functions, including cell shape, motility, and intracellular trafficking. In proliferating cells, they are essential components in the division process through the formation of the mitotic spindle. As a result of these functions, tubulin and microtubules are targets for anticancer agents. Microtubule-targeting agents can be divided into two groups: microtubule-stabilizing, and microtubule-destabilizing agents. The former bind to the tubulin polymer and stabilize microtubules, while the latter bind to the tubulin dimers and destabilize microtubules. Alteration of tubulin-microtubule equilibrium determines th…
Novel Approaches for Glioblastoma Treatment: Focus on Tumor Heterogeneity, Treatment Resistance, and Computational Tools
2019
BACKGROUND: Glioblastoma (GBM) is a highly aggressive primary brain tumor. Currently, the suggested line of action is the surgical resection followed by radiotherapy and treatment with the adjuvant temozolomide (TMZ), a DNA alkylating agent. However, the ability of tumor cells to deeply infiltrate the surrounding tissue makes complete resection quite impossible, and in consequence, the probability of tumor recurrence is high, and the prognosis is not positive. GBM is highly heterogeneous and adapts to treatment in most individuals. Nevertheless, these mechanisms of adaption are unknown. RECENT FINDINGS: In this review, we will discuss the recent discoveries in molecular and cellular heterog…
The ARF GAPs ELMOD1 and ELMOD3 act at the Golgi and cilia to regulate ciliogenesis and ciliary protein traffic
2022
ELMODs are a family of three mammalian paralogs that display GTPase activating protein (GAP) activity towards a uniquely broad array of ADP-ribosylation factor (ARF) family GTPases that includes ARF-like (ARL) proteins. ELMODs are ubiquitously expressed in mammalian tissues, highly conserved across eukaryotes, and ancient in origin, being present in the last eukaryotic common ancestor. We described functions of ELMOD2 in immortalized mouse embryonic fibroblasts (MEFs) in the regulation of cell division, microtubules, ciliogenesis, and mitochondrial fusion. Here, using similar strategies with the paralogs ELMOD1 and ELMOD3, we identify novel functions and locations of these cell regulators a…
The translocation of signaling molecules in dark adapting mammalian rod photoreceptor cells is dependent on the cytoskeleton.
2008
In vertebrate rod photoreceptor cells, arrestin and the visual G-protein transducin move between the inner segment and outer segment in response to changes in light. This stimulus dependent translocation of signalling molecules is assumed to participate in long term light adaptation of photoreceptors. So far the cellular basis for the transport mechanisms underlying these intracellular movements remains largely elusive. Here we investigated the dependency of these movements on actin filaments and the microtubule cytoskeleton of photoreceptor cells. Co-cultures of mouse retina and retinal pigment epithelium were incubated with drugs stabilizing and destabilizing the cytoskeleton. The actin a…