共查询到20条相似文献,搜索用时 88 毫秒
1.
Diego Reginensi Patricia Carulla Sara Nocentini Oscar Seira Abel Torres-Espín Andreu Matamoros-Angles Rosalina Gavín María Teresa Moreno-Flores Francisco Wandosell Josep Samitier Xavier Trepat Xavier Navarro José Antonio del Río 《Cellular and molecular life sciences : CMLS》2015,72(14):2719-2737
Olfactory ensheathing cell (OEC) transplantation emerged some years ago as a promising therapeutic strategy to repair injured spinal cord. However, inhibitory molecules are present for long periods of time in lesioned spinal cord, inhibiting both OEC migration and axonal regrowth. Two families of these molecules, chondroitin sulphate proteoglycans (CSPG) and myelin-derived inhibitors (MAIs), are able to trigger inhibitory responses in lesioned axons. Mounting evidence suggests that OEC migration is inhibited by myelin. Here we demonstrate that OEC migration is largely inhibited by CSPGs and that inhibition can be overcome by the bacterial enzyme Chondroitinase ABC. In parallel, we have generated a stable OEC cell line overexpressing the Nogo receptor (NgR) ectodomain to reduce MAI-associated inhibition in vitro and in vivo. Results indicate that engineered cells migrate longer distances than unmodified OECs over myelin or oligodendrocyte-myelin glycoprotein (OMgp)-coated substrates. In addition, they also show improved migration in lesioned spinal cord. Our results provide new insights toward the improvement of the mechanisms of action and optimization of OEC-based cell therapy for spinal cord lesion. 相似文献
2.
Windus LC Chehrehasa F Lineburg KE Claxton C Mackay-Sim A Key B St John JA 《Cellular and molecular life sciences : CMLS》2011,68(19):3233-3247
Axons of primary olfactory neurons are intimately associated with olfactory ensheathing cells (OECs) from the olfactory epithelium until the final targeting of axons within the olfactory bulb. However, little is understood about the nature and role of interactions between OECs and axons during development of the olfactory nerve pathway. We have used high resolution time-lapse microscopy to examine the growth and interactions of olfactory axons and OECs in vitro. Transgenic mice expressing fluorescent reporters in primary olfactory axons (OMP-ZsGreen) and ensheathing cells (S100ß-DsRed) enabled us to selectively analyse these cell types in explants of olfactory epithelium. We reveal here that rather than providing only a permissive substrate for axon growth, OECs play an active role in modulating the growth of pioneer olfactory axons. We show that the interactions between OECs and axons were dependent on lamellipodial waves on the shaft of OEC processes. The motility of OECs was mediated by GDNF, which stimulated cell migration and increased the apparent motility of the axons, whereas loss of OECs via laser ablation of the cells inhibited olfactory axon outgrowth. These results demonstrate that the migration of OECs strongly regulates the motility of axons and that stimulation of OEC motility enhances axon extension and growth cone activity. 相似文献
3.
Angela Dittmer Kristina Hohlfeld Jana Lützkendorf Lutz P. Müller Jürgen Dittmer 《Cellular and molecular life sciences : CMLS》2009,66(18):3053-3065
Mesenchymal stem cells (MSCs) have been shown to communicate with tumor cells. We analyzed the effect of human MSCs (hMSCs)
on breast cancer cells in three-dimensional cultures. By using GFP expression and immunohistochemistry, we show that hMSCs
invade 3D breast cancer cell aggregates. hMSCs caused breast cancer spheroids to become disorganized which was accompanied
by a disruption of cell–cell adhesion, E-cadherin cleavage, and nuclear translocation of E-cadherin, but not by epithelial/mesenchymal
transition or by an increase in ERK1/2 activity. In addition, hMSCs enhanced the motility of breast cancer cells. Inhibition
of ADAM10 (a disintegrin and metalloprotease 10), known to cleave E-cadherin, prevented both hMSC-mediated E-cadherin cleavage
and enhanced migration. Our data suggest that hMSCs interfere with cell–cell adhesion and enhance migration of breast cancer
cells by activating ADAM10. 相似文献
4.
Olfactory ensheathing cell phenotype following implantation in the lesioned spinal cord 总被引:5,自引:2,他引:3
Woodhall E West AK Vickers JC Chuah MI 《Cellular and molecular life sciences : CMLS》2003,60(10):2241-2253
5.
Lamellipodia mediate the heterogeneity of central olfactory ensheathing cell interactions 总被引:2,自引:2,他引:0
Louisa C. E. Windus Katie E. Lineburg Susan E. Scott Christina Claxton Alan Mackay-Sim Brian Key James A. St John 《Cellular and molecular life sciences : CMLS》2010,67(10):1735-1750
The growth and guidance of primary olfactory axons are partly attributed to the presence of olfactory ensheathing cells (OECs). However, little is understood about the differences between the subpopulations of OECs and what regulates their interactions. We used OEC-axon assays and determined that axons respond differently to peripheral and central OECs. We then further purified OECs from anatomically distinct regions of the olfactory bulb. Cell behaviour assays revealed that OECs from the olfactory bulb were a functionally heterogeneous population with distinct differences which is consistent with their proposed roles in vivo. We found that the heterogeneity was regulated by motile lamellipodial waves along the shaft of the OECs and that inhibition of lamellipodial wave activity via Mek1 abolished the ability of the cells to distinguish between each other. These results demonstrate that OECs from the olfactory bulb are a heterogeneous population that use lamellipodial waves to regulate cell–cell recognition. 相似文献
6.
E-cadherin plays an essential role in collective directional migration of large epithelial sheets 总被引:1,自引:1,他引:0
Li L Hartley R Reiss B Sun Y Pu J Wu D Lin F Hoang T Yamada S Jiang J Zhao M 《Cellular and molecular life sciences : CMLS》2012,69(16):2779-2789
In wound healing and development, large epithelial sheets migrate collectively, in defined directions, and maintain tight cell-cell adhesion. This type of movement ensures an essential function of epithelia, a barrier, which is lost when cells lose connection and move in isolation. Unless wounded, epithelial sheets in cultures normally do not have overall directional migration. Cell migration is mostly studied when cells are in isolation and in the absence of mature cell-cell adhesion; the mechanisms of the migration of epithelial sheets are less well understood. We used small electric fields (EFs) as a directional cue to instigate and guide migration of epithelial sheets. Significantly, cells in monolayer migrated far more efficiently and directionally than cells in isolation or smaller cell clusters. We demonstrated for the first time the group size-dependent directional migratory response in several types of epithelial cells. Gap junctions made a minimal contribution to the directional collective migration. Breaking down calcium-dependent cell-cell adhesion significantly reduced directional sheet migration. Furthermore, E-cadherin blocking antibodies abolished migration of cell sheets. Traction force analysis revealed an important role of forces that cells in the leading rows exert on the substratum. With EF, the traction forces of the leading edge cells coordinated in directional re-orientation. Our study thus identifies a novel mechanism--E-cadherin dependence and coordinated traction forces of leading cells in collective directional migration of large epithelial sheets. 相似文献
7.
Ken-ichi Nakahama 《Cellular and molecular life sciences : CMLS》2010,67(23):4001-4009
Cellular communication between the bone component cells osteoblasts, osteocytes and (pre-)osteoclasts is essential for bone
remodeling which maintains bone integrity. As in the remodeling of other organs, cell death is a trigger for remodeling of
bone. During the systematic process of bone remodeling, direct or indirect cell–cell communication is indispensable. Thus,
osteoblasts induce migration and differentiation of preosteoclasts, which is followed by bone resorption (by mature multinuclear
osteoclasts). After completion of bone resorption, apoptosis of mature osteoclasts and differentiation of osteoblasts are
initiated. At this time, the osteoblasts do not support osteoclast differentiation but do support bone formation. Finally,
osteoblasts differentiate to osteocytes in bone or to bone lining cells on bone surfaces. In this way, old bone areas are
regenerated as new bone. In this review the role of cell–cell communication in bone remodeling is discussed. 相似文献
8.
Agnès Thierry Bernard Dujon Guy-Franck Richard 《Cellular and molecular life sciences : CMLS》2010,67(5):671-676
Megasatellites are DNA tandem arrays made of large motifs; they were discovered in the yeast Candida
glabrata. They are widespread in this species (40 copies) but are not found in any other hemiascomycete so far, raising the intriguing
question of their origin. They are found mainly in genes encoding cell wall products, suggesting that megasatellites were
selected for a function linked to cell–cell adhesion or to pathogenicity. Their putative role in promoting genome rearrangements
by interfering with DNA replication will also be discussed. 相似文献
9.
Differential roles of multiple adhesion molecules in cell migration: granule cell migration in cerebellum 总被引:2,自引:0,他引:2
C M Chuong 《Experientia》1990,46(9):892-899
The migration of cerebellar granule cells from the external granular layer to the internal granular layer is mediated by the radical Bergmann glial fiber. Recent works have shown that cell adhesion molecules, extra-cellular matrix proteins and proteolytic enzymes or their activators are involved in this process. Immuno-localization studies showed differential temporal and spatial expression patterns of different adhesion molecules, their isoforms, and post-translational modification during different stages of granule cell migration. Functional perturbation experiments using cerebellar explant cultures demonstrated that several adhesion molecules as well as plasminogen activator are involved in granule cell migration and are required in different stages. Other systems used to study granule cell migration including dissociated microwell cultures and granule cell deficient mouse mutants are discussed in the context of adhesion molecules. The results accumulated so far suggest that the migration of granule cells is a complex process in which the cooperation of a group of molecules with different functions, some for adhesion some for de-adhesion, are required to fulfill the different needs during the migratory course. 相似文献
10.
C. -M. Chuong 《Cellular and molecular life sciences : CMLS》1990,46(9):892-899
Summary The migration of cerebellar granule cells from the external granular layer to the internal granular layer is mediated by the radial Bergmann glial fiber. Recent works have shown that cell adhesion molecules, extra-cellular matrix proteins and proteolytic enzymes or their activators are involved in this process. Immuno-localization studies showed differential temporal and spatial expression patterns of different adhesion molecules, their isoforms, and post-translational modification during different stages of granule cell migration. Functional perturbation experiments using cerebellar explant cultures demonstrated that several adhesion molecules as well as plasminogen activator are involved in granule cell migration and are required in different stages. Other systems used to study granule cell migration including dissociated microwell cultures and granule cell deficient mouse mutants are discussed in the context of adhesion molecules. The results accumulated so far suggest that the migration of granule cells is a complex process in which the cooperation of a group of molecules with different functions, some for adhesion some for de-adhesion, are required to fulfill the different needs during the migratory course. 相似文献
11.
The murine epidermis contains resident T cells that express a canonical γδ TCR and arise from fetal thymic precursors. These
cells are termed dendritic epidermal T cells (DETC) and use a TCR that is restricted to the skin in adult animals. DETC produce
low levels of cytokines and growth factors that contribute to epidermal homeostasis. Upon activation, DETC can secrete large
amounts of inflammatory molecules which participate in the communication between DETC, neighboring keratinocytes and langerhans
cells. Chemokines produced by DETC may recruit inflammatory cells to the epidermis. In addition, cell–cell mediated immune
responses also appear important for epidermal–T cell communication. Information is provided which supports a crucial role
for DETC in inflammation, wound healing, and tumor surveillance. 相似文献
12.
Endogenous electrical fields (EFs) at corneal and skin wounds send a powerful signal that directs cell migration during wound
healing. This signal therefore may serve as a fundamental regulator directing cell polarization and migration. Very little
is known of the intracellular and molecular mechanisms that mediate EF-induced cell polarization and migration. Here, we report
that Chinese hamster ovary (CHO) cells show robust directional polarization and migration in a physiological EF (0.3–1 V/cm)
in both dissociated cell culture and monolayer culture. An EF of 0.6 V/cm completely abolished cell migration into wounds
in monolayer culture. An EF of higher strength (≥1 V/cm) is an overriding guidance cue for cell migration. Application of
EF induced quick phosphorylation of glycogen synthase kinase 3β (GSK-3β) which reached a peak as early as 3 min in an EF.
Inhibition of protein kinase C (PKC) significantly reduced EF-induced directedness of cell migration initially (in 1–2 h).
Inhibition of GSK-3β completely abolished EF-induced GA polarization and significantly inhibited the directional cell migration,
but at a later time (2–3 h in an EF). Those results suggest that GSK-3β is essential for physiological EF-induced Golgi apparatus
(GA) polarization and optimal electrotactic cell migration. 相似文献
13.
Rocío Aguilar-Cuenca Alba Juanes-García Miguel Vicente-Manzanares 《Cellular and molecular life sciences : CMLS》2014,71(3):479-492
Mechanotransduction encompasses the role of mechanical forces in controlling cell behavior by activating signal transduction pathways. Most forces at a cellular level are caused by myosin II, which contracts and cross-links actin. Myosin II-dependent forces are transmitted through the actin cytoskeleton to molecular endpoints that promote specific cellular outcomes, e.g., cell proliferation, adhesion, or migration. For example, most adhesive and migratory phenomena are mechanically linked by a molecular clutch comprised of mechanosensitive scaffolds. Myosin II activation and mechanosensitive molecular mechanisms are finely tuned and spatiotemporally integrated to coordinate morphogenetic events during development. Mechanical events dependent on myosin II also participate in tumor cell proliferation, invasion, and metastatic dissemination. Specifically, tumor cells alter the mechanical properties of the microenvironment to create favorable conditions for proliferation and/or dissemination. These observations position myosin II-dependent force generation and mechanotransduction at the crossroads between normal development and cancer. 相似文献
14.
Strotmann J 《Cellular and molecular life sciences : CMLS》2001,58(4):531-537
Olfactory sensory neurons detect an enormous variety of small volatile molecules with extremely high sensitivity and specificity.
The actual recognition and discrimination of odorous compounds is accomplished by specific receptor proteins located in the
ciliary membrane of the sensory neurons. Axonal connections into the olfactory bulb, the first relay station for odor processing
in the brain, are organized such that all neurons expressing the same odorant receptor converge their axons onto common glomeruli
which are located at similar positions in all individuals from one species. For the establishment of this precise targeting
of olfactory axons to their appropriate glomeruli, combinatorial functions of axon-associated cell adhesion molecules and
odorant receptor proteins appear to be required. Odorants that stimulate distinct receptor cell populations will thereby activate
a specific combination of glomeruli in the bulb; this characteristic activity pattern may be used by the system to encode
the quality of a particular odorant. 相似文献
15.
Aniko Keller-Pinter Sandor Bottka Jozsef Timar Janina Kulka Robert Katona Laszlo Dux Ferenc Deak Laszlo Szilak 《Cellular and molecular life sciences : CMLS》2010,67(11):1881-1894
During mitosis, cells detach, and the cell–matrix interactions become restricted. At the completion of cytokinesis, the two
daughter cells are still connected transiently by an intercellular bridge (ICB), which is subjected to abscission, as the
terminal step of cytokinesis. Cell adhesion to the matrix is mediated by syndecan-4 (SDC4) transmembrane heparan sulfate proteoglycan.
Our present work demonstrated that SDC4 promotes cytokinesis in a phosphorylation-dependent manner in MCF-7 breast adenocarcinoma
cells. The serine179-phosphorylation and the ectodomain shedding of SDC4 changed periodically in a cell cycle-dependent way
reaching the maximum at G2/M phases. On the contrary, the phospho-resistant Ser179Ala mutant abrogated the shedding. The phosphorylated
full-length and shed remnants enriched along the mitotic spindles, and subsequently in the ICBs, however, proper membrane
insertion was necessary for midbody localization. Expression of phosphomimicking Ser179Glu SDC4 resulted in incomplete abscission,
whereas expression of the phospho-resistant SDC4 led to giant, multinucleated cells. 相似文献
16.
Bryan A. Nerger Michael J. Siedlik Celeste M. Nelson 《Cellular and molecular life sciences : CMLS》2017,74(10):1819-1834
Cell-generated forces drive an array of biological processes ranging from wound healing to tumor metastasis. Whereas experimental techniques such as traction force microscopy are capable of quantifying traction forces in multidimensional systems, the physical mechanisms by which these forces induce changes in tissue form remain to be elucidated. Understanding these mechanisms will ultimately require techniques that are capable of quantifying traction forces with high precision and accuracy in vivo or in systems that recapitulate in vivo conditions, such as microfabricated tissues and engineered substrata. To that end, here we review the fundamentals of traction forces, their quantification, and the use of microfabricated tissues designed to study these forces during cell migration and tissue morphogenesis. We emphasize the differences between traction forces in two- and three-dimensional systems, and highlight recently developed techniques for quantifying traction forces. 相似文献
17.
Eleonora Dondossola Anna Gasparri Angela Bachi Renato Longhi Marie-Hélène Metz-Boutigue Bruno Tota Karen B. Helle Flavio Curnis Angelo Corti 《Cellular and molecular life sciences : CMLS》2010,67(12):2107-2118
Fibroblast adhesion can be modulated by proteins released by neuroendocrine cells and neurons, such as chromogranin A (CgA)
and its N-terminal fragment vasostatin-1 (VS-1, CgA1–78). We have investigated the mechanisms of the interaction of VS-1 with fibroblasts and of its pro-adhesive activity and have
found that the proadhesive activity of VS-1 relies on its interaction with the fibroblast membrane via a phospholipid-binding
amphipathic α-helix located within residues 47–66, as well as on the interaction of the adjacent C-terminal region 67–78,
which is structurally similar to ezrin–radixin–moesin-binding phosphoprotein 50 (a membrane-cytoskeleton adapter protein),
with other cellular components critical for the regulation of cell cytoskeleton. 相似文献
18.
K. Paňková D. Rösel M. Novotný Jan Brábek 《Cellular and molecular life sciences : CMLS》2010,67(1):63-71
Tumor cells exhibit at least two distinct modes of migration when invading the 3D environment. A single tumor cell’s invasive
strategy follows either mesenchymal or amoeboid patterns. Certain cell types can use both modes of invasiveness and undergo
transitions between them. This work outlines the signaling pathways involved in mesenchymal and amoeboid types of tumor cell
motility and summarizes the molecular mechanisms that are involved in transitions between them. The focus is on the signaling
of the Rho family of small GTPases that regulate the cytoskeleton-dependent processes taking place during the cell migration.
The multiple interactions among the Rho family of proteins, their regulators and effectors are thought to be the key determinants
of the particular type of invasiveness. Mesenchymal and amoeboid invasive strategies display different adhesive and proteolytical
interactions with the surrounding matrix and the alterations influencing these interactions can also lead to the transitions. 相似文献
19.
Simms RJ Hynes AM Eley L Inglis D Chaudhry B Dawe HR Sayer JA 《Cellular and molecular life sciences : CMLS》2012,69(6):993-1009
Joubert syndrome and related diseases (JSRD) are cerebello-oculo-renal syndromes with phenotypes including cerebellar hypoplasia,
retinal dystrophy, and nephronophthisis (a cystic kidney disease). Mutations in AHI1 are the most common genetic cause of JSRD, with developmental hindbrain anomalies and retinal degeneration being prominent
features. We demonstrate that Ahi1, a WD40 domain-containing protein, is highly conserved throughout evolution and its expression
associates with ciliated organisms. In zebrafish ahi1 morphants, the phenotypic spectrum of JSRD is modeled, with embryos showing brain, eye, and ear abnormalities, together with
renal cysts and cloacal dilatation. Following ahi1 knockdown in zebrafish, we demonstrate loss of cilia at Kupffer’s vesicle and subsequently defects in cardiac left–right
asymmetry. Finally, using siRNA in renal epithelial cells we demonstrate a role for Ahi1 in both ciliogenesis and cell–cell
junction formation. These data support a role for Ahi1 in epithelial cell organization and ciliary formation and explain the
ciliopathy phenotype of AHI1 mutations in man. 相似文献
20.
Myelin basic protein: a multifunctional protein 总被引:1,自引:1,他引:0
Boggs JM 《Cellular and molecular life sciences : CMLS》2006,63(17):1945-1961
Myelin basic protein (MBP), the second most abundant protein in central nervous system myelin, is responsible for adhesion
of the cytosolic surfaces of multilayered compact myelin. A member of the ‘intrinsically disordered’ or conformationally adaptable
protein family, it also appears to have several other functions. It can interact with a number of polyanionic proteins including
actin, tubulin, Ca2+-calmodulin, and clathrin, and negatively charged lipids, and acquires structure on binding to them. It may act as a membrane
actin-binding protein, which might allow it to participate in transmission of extracellular signals to the cytoskeleton in
oligodendrocytes and tight junctions in myelin. Some size isoforms of MBP are transported into the nucleus and thus they may
also bind polynucleotides. Extracellular signals received by myelin or cultured oligodendrocytes cause changes in phosphorylation
of MBP, suggesting that MBP is also involved in signaling. Further study of this very abundant protein will reveal how it
is utilized by the oligodendrocyte and myelin for different purposes.
Received 2 March 2006; received after revision 12 April 2006; accepted 16 May 2006 相似文献