scholarly journals Synaptotagmin 13 orchestrates pancreatic endocrine cell egression and islet morphogenesis

2021 ◽  
Author(s):  
Mostafa Bakhti ◽  
Aimée Bastidas-Ponce ◽  
Sophie Tritschler ◽  
Marta Tarquis-Medina ◽  
Eva Nedvedova ◽  
...  
Keyword(s):  
Endocrine Cell ◽  
Cancer Metastasis ◽  
Leading Edge ◽  
Diabetes Therapy ◽  
Acetylated Tubulin ◽  
Cell Matrix ◽  
Resolution Imaging ◽  
Key Driver ◽  
Cell Matrix Adhesion

AbstractEpithelial cell egression is important for organ development, but also drives cancer metastasis. Better understandings of pancreatic epithelial morphogenetic programs generating islets of Langerhans aid to diabetes therapy. Here we identify the Ca2+-independent atypical Synaptotagmin 13 (Syt13) as a key driver of endocrine cell egression and islet formation. We detected upregulation of Syt13 in endocrine precursors that correlates with increased expression of unique cytoskeletal components. High-resolution imaging reveals a previously unidentified apical-basal to front-rear repolarization during endocrine cell egression. Strikingly, Syt13 interacts with acetylated tubulin and phosphatidylinositol phospholipids and localizes to the leading-edge of egressing cells. Knockout of Syt13 impairs endocrine cell egression and skews the α- to-β-cell ratio. Mechanistically, Syt13 regulates endocytosis to remodel the basement membrane and cell-matrix adhesion at the leading-edge of egressing endocrine cells. Altogether, these findings implicate an unexpected role of Syt13 in regulating cell polarity to orchestrate endocrine cell egression and islet morphogenesis.

Hierarchical assembly of cell–matrix adhesion complexes

2004 ◽  
Vol 32 (3) ◽  
pp. 416-420 ◽  
Author(s):  
R. Zaidel-Bar ◽  
M. Cohen ◽  
L. Addadi ◽  
B. Geiger
Keyword(s):  
Extracellular Matrix ◽  
Cell Surface ◽  
Focal Adhesions ◽  
Leading Edge ◽  
Cellular Migration ◽  
Hierarchical Assembly ◽  
Surface Recognition ◽  
Cell Matrix ◽  
Molecular Events ◽  
Cell Matrix Adhesion

The adhesion of cells to the extracellular matrix is a dynamic process, mediated by a series of cell-surface and matrix-associated molecules that interact with each other in a spatially and temporally regulated manner. These interactions play a major role in tissue formation, cellular migration and the induction of adhesion-mediated transmembrane signals. In this paper, we show that the formation of matrix adhesions is a hierarchical process, consisting of several sequential molecular events. One of the earliest steps in surface recognition is mediated, in some cells, by a 1 μm-thick cell-surface hyaluronan coat, which precedes the establishment of stable, cytoskeleton-associated adhesions. The earliest forms of these integrin-mediated contacts are dot-shaped FXs (focal complexes), which are formed under the protrusive lamellipodium of migrating cells. These adhesions recruit, sequentially, different anchor proteins that are involved in binding the actin cytoskeleton to the membrane. Conspicuous in its absence from FXs is zyxin, which is recruited to these sites only on retraction of the leading edge and the transformation of the FXs into a focal adhesion. Continuing application of force to focal adhesions results in the formation of fibrillar adhesions and reorganization of the extracellular matrix. The formation of these adhesions depends on actomyosin contractility and matrix pliability.

scholarly journals Cellular and molecular partners involved in gut morphogenesis and differentiation

1998 ◽  
Vol 353 (1370) ◽  
pp. 847-856 ◽  
Author(s):  
M. Kedinger ◽  
O. Lefebvre ◽  
I. Duluc ◽  
J. N. Freund ◽  
P. Simon–Assmann
Keyword(s):  
Cross Talk ◽  
Mesenchymal Cell ◽  
Cell Compartment ◽  
Paracrine Factors ◽  
Cell Matrix ◽  
Epithelial Cell Migration ◽  
Extracellular Matrix Molecules ◽  
Proliferation And Differentiation ◽  
Cell Matrix Adhesion

The intestinal mucosa represents an interesting model to study the cellular and molecular basis of epithelial–mesenchymal cross–talk participating in the development and maintenance of the digestive function. This cross–talk involves extracellular matrix molecules, cell–cell and cell–matrix adhesion molecules as well as paracrine factors and their receptors. The cellular and molecular unit is additionally regulated by hormonal, immune and neural inputs. Such integrated cell interactions are involved in pattern formation, in proximodistal regionalization, in maintenance of a gradient of epithelial proliferation and differentiation, and in epithelial cell migration. We focus predominantly on two aspects of these integrated interactions in this paper: (i) the role of basement membrane molecules, namely laminins, in the developmental and spatial epithelial behaviour; and (ii) the importance of the mesenchymal cell compartment in these processes.

scholarly journals Perturbing integrin function inhibits microtubule growth from centrosomes, spindle assembly, and cytokinesis

2006 ◽  
Vol 174 (4) ◽  
pp. 491-497 ◽  
Author(s):  
Carlos G. Reverte ◽  
Angela Benware ◽  
Christopher W. Jones ◽  
Susan E. LaFlamme
Keyword(s):  
Mitotic Spindle ◽  
Cell Types ◽  
Cellular Systems ◽  
Integrin Β1 ◽  
Dynamic Changes ◽  
Matrix Adhesion ◽  
Cell Matrix ◽  
Microtubule Growth ◽  
Cell Matrix Adhesion

In many mammalian cell types, integrin-mediated cell-matrix adhesion is required for the G1–S transition of the cell cycle. As cells approach mitosis, a dramatic remodeling of their cytoskeleton accompanies dynamic changes in matrix adhesion, suggesting a mechanistic link. However, the role of integrins in cell division remains mostly unexplored. Using two cellular systems, we demonstrate that a point mutation in the β1 cytoplasmic domain (β1 tail) known to decrease integrin activity supports entry into mitosis but inhibits the assembly of a radial microtubule array focused at the centrosome during interphase, the formation of a bipolar spindle at mitosis and cytokinesis. These events are restored by externally activating the mutant integrin with specific antibodies. This is the first demonstration that the integrin β1 tail can regulate centrosome function, the assembly of the mitotic spindle, and cytokinesis.

scholarly journals Ca2+/H+ exchange by acidic organelles regulates cell migration in vivo

2016 ◽  
Vol 212 (7) ◽  
pp. 803-813 ◽  
Author(s):  
Manuela Melchionda ◽  
Jon K. Pittman ◽  
Roberto Mayor ◽  
Sandip Patel
Keyword(s):  
Cell Migration ◽  
Neural Crest ◽  
Cell Matrix ◽  
Physiological Relevance ◽  
Underlying Mechanisms ◽  
Acidic Organelles ◽  
Cell Matrix Adhesion ◽  
Insight Into

Increasing evidence implicates Ca2+ in the control of cell migration. However, the underlying mechanisms are incompletely understood. Acidic Ca2+ stores are fast emerging as signaling centers. But how Ca2+ is taken up by these organelles in metazoans and the physiological relevance for migration is unclear. Here, we identify a vertebrate Ca2+/H+ exchanger (CAX) as part of a widespread family of homologues in animals. CAX is expressed in neural crest cells and required for their migration in vivo. It localizes to acidic organelles, tempers evoked Ca2+ signals, and regulates cell-matrix adhesion during migration. Our data provide new molecular insight into how Ca2+ is handled by acidic organelles and link this to migration, thereby underscoring the role of noncanonical Ca2+ stores in the control of Ca2+-dependent function.

scholarly journals The integrin cytoplasmic domain-associated protein ICAP-1 binds and regulates Rho family GTPases during cell spreading

2002 ◽  
Vol 156 (2) ◽  
pp. 377-388 ◽  
Author(s):  
Simona Degani ◽  
Fiorella Balzac ◽  
Mara Brancaccio ◽  
Simona Guazzone ◽  
Saverio Francesco Retta ◽  
...  
Keyword(s):  
Cell Spreading ◽  
Cytoplasmic Domain ◽  
Nih3t3 Cells ◽  
Cell Matrix ◽  
Rho Family Gtpases ◽  
Rho Family ◽  
First Time ◽  
Cell Matrix Adhesion

Using two-hybrid screening, we isolated the integrin cytoplasmic domain-associated protein (ICAP-1), an interactor for the COOH terminal region of the β1A integrin cytoplasmic domain. To investigate the role of ICAP-1 in integrin-mediated adhesive function, we expressed the full-length molecule in NIH3T3 cells. ICAP-1 expression strongly prevents NIH3T3 cell spreading on extracellular matrix. This inhibition is transient and can be counteracted by coexpression of a constitutively activated mutant of Cdc42, suggesting that ICAP-1 acts upstream of this GTPase. In addition, we found that ICAP-1 binds both to Cdc42 and Rac1 in vitro, and its expression markedly inhibits activation of these GTPases during integrin-mediated cell adhesion to fibronectin as detected by PAK binding assay. In the attempt to define the molecular mechanism of this inhibition, we show that ICAP-1 reduces both the intrinsic and the exchange factor–induced dissociation of GDP from Cdc42; moreover, purified ICAP-1 displaces this GTPase from cellular membranes. Together, these data show for the first time that ICAP-1 regulates Rho family GTPases during integrin-mediated cell matrix adhesion, acting as guanine dissociation inhibitor.

Role of extracellular matrix in regulating embryonic epithelial-mesenchymal transition

2012 ◽  
Vol 3 (4) ◽  
pp. 333-344
Author(s):  
Francesca Zito
Keyword(s):  
Extracellular Matrix ◽  
Epithelial Mesenchymal Transition ◽  
Membrane Receptors ◽  
Mesenchymal Transition ◽  
Functional Studies ◽  
Cell Matrix ◽  
Fibrotic Diseases ◽  
Cell Matrix Adhesion ◽  
Specific Membrane

AbstractEmbryogenesis and morphogenesis are characterized by complex cell rearrangements and movements which require appropriate interactions of cells with the surrounding extracellular matrix (ECM) by means of specific membrane receptors. Interest in the identification and purification of ECM components, as well as in conducting functional studies of them, including their ligands and other molecules involved in cell-matrix adhesion, has intensified in recent years, increasing our knowledge of developmental machinery. Cellular movements play an important role during the epithelial-mesenchymal transition (EMT) events, which are key processes in normal embryogenesis as well as in pathological conditions, such as fibrotic diseases and cancer. Thus, to more fully understand mechanisms underlying the EMT process, and for better knowledge of the embryonic defects related to this process, it would be useful to study the substrates on which EMT cells move during embryo development. This review focuses on a few different embryonic systems, taking into account the cell migration that occurs during EMT and highlighting, in particular, studies describing the direct involvement of ECM molecules.

Podokinesis in endothelial cell migration: role of nitric oxide

1998 ◽  
Vol 274 (1) ◽  
pp. C236-C244 ◽  
Author(s):  
Eisei Noiri ◽  
Eugene Lee ◽  
Jacqueline Testa ◽  
James Quigley ◽  
David Colflesh ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Endothelial Cell ◽  
No Synthase ◽  
Endothelial Cell Migration ◽  
Guidance Cues ◽  
Cell Matrix ◽  
Cell Matrix Adhesion

Previously, we demonstrated the role of nitric oxide (NO) in transforming epithelial cells from a stationary to locomoting phenotype [E. Noiri, T. Peresleni, N. Srivastava, P. Weber, W. F. Bahou, N. Peunova, and M. S. Goligorsky. Am. J. Physiol. 270 ( Cell Physiol. 39): C794–C802, 1996] and its permissive function in endothelin-1-stimulated endothelial cell migration (E. Noiri, Y. Hu, W. F. Bahou, C. Keese, I. Giaever, and M. S. Goligorsky. J. Biol. Chem. 272: 1747–1753, 1997). In the present study, the role of functional NO synthase in executing the vascular endothelial growth factor (VEGF)-guided program of endothelial cell migration and angiogenesis was studied in two independent experimental settings. First, VEGF, shown to stimulate NO release from simian virus 40-immortalized microvascular endothelial cells, induced endothelial cell transwell migration, whereas N G-nitro-l-arginine methyl ester (l-NAME) or antisense oligonucleotides to endothelial NO synthase suppressed this effect of VEGF. Second, in a series of experiments on endothelial cell wound healing, the rate of VEGF-stimulated cell migration was significantly blunted by the inhibition of NO synthesis. To gain insight into the possible mode of NO action, we next addressed the possibility that NO modulates cell matrix adhesion by performing impedance analysis of endothelial cell monolayers subjected to NO. The data showed the presence of spontaneous fluctuations of the resistance in ostensibly stationary endothelial cells. Spontaneous oscillations were induced by NO, which also inhibited cell matrix adhesion. This process we propose to term “podokinesis” to emphasize a scalar form of micromotion that, in the presence of guidance cues, e.g., VEGF, is transformed to a vectorial movement. In conclusion, execution of the program for directional endothelial cell migration requires two coexisting messages: NO-induced podokinesis (scalar motion) and guidance cues, e.g., VEGF, which imparts a vectorial component to the movement. Such a requirement for the dual signaling may explain a mismatch in the demand and supply with newly formed vessels in different pathological states accompanied by the inhibition of NO synthase.

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