scholarly journals Kindlin-2 recruits paxillin and Arp2/3 to promote membrane protrusions during initial cell spreading

2017 ◽  
Vol 216 (11) ◽  
pp. 3785-3798 ◽  
Author(s):  
Ralph T. Böttcher ◽  
Maik Veelders ◽  
Pascaline Rombaut ◽  
Jan Faix ◽  
Marina Theodosiou ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Adaptor Protein ◽  
Cell Spreading ◽  
Dual Role ◽  
Membrane Protrusion ◽  
Pleckstrin Homology ◽  
Initial Cell ◽  
Membrane Protrusions ◽  
Lamellipodia Formation

Cell spreading requires the coupling of actin-driven membrane protrusion and integrin-mediated adhesion to the extracellular matrix. The integrin-activating adaptor protein kindlin-2 plays a central role for cell adhesion and membrane protrusion by directly binding and recruiting paxillin to nascent adhesions. Here, we report that kindlin-2 has a dual role during initial cell spreading: it binds paxillin via the pleckstrin homology and F0 domains to activate Rac1, and it directly associates with the Arp2/3 complex to induce Rac1-mediated membrane protrusions. Consistently, abrogation of kindlin-2 binding to Arp2/3 impairs lamellipodia formation and cell spreading. Our findings identify kindlin-2 as a key protein that couples cell adhesion by activating integrins and the induction of membrane protrusions by activating Rac1 and supplying Rac1 with the Arp2/3 complex.

Dystroglycan: a multifunctional adaptor protein

2005 ◽  
Vol 33 (6) ◽  
pp. 1254-1255 ◽  
Author(s):  
J.R. Higginson ◽  
S.J. Winder
Keyword(s):  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Cell Signalling ◽  
Adaptor Protein ◽  
Interacting Proteins ◽  
Cytoskeleton Reorganization ◽  
Membrane Spanning ◽  
New Research

Dystroglycan, a ubiquitous membrane-spanning cell adhesion molecule, is a crucial link between the actin cytoskeleton and the extracellular matrix. With a wide expression pattern and multiple interacting proteins, not only is dystroglycan now thought to be important as a structural molecule but also new research has suggested that it has a role in cell signalling, cytoskeleton reorganization and as a potential tumour suppressor.

scholarly journals Functionally distinct laminin receptors mediate cell adhesion and spreading: the requirement for surface galactosyltransferase in cell spreading.

1988 ◽  
Vol 107 (5) ◽  
pp. 1863-1871 ◽  
Author(s):  
R B Runyan ◽  
J Versalovic ◽  
B D Shur
Keyword(s):  
Cell Adhesion ◽  
Cell Surface ◽  
Molecular Mechanisms ◽  
Cell Attachment ◽  
Cell Spreading ◽  
Biological Properties ◽  
Initial Cell ◽  
Laminin Receptors ◽  
Mediate Cell ◽  
A Chain

The molecular mechanisms underlying cell attachment and subsequent cell spreading on laminin are shown to be distinct form one another. Cell spreading is dependent upon the binding of cell surface galactosyltransferase (GalTase) to laminin oligosaccharides, while initial cell attachment to laminin occurs independent of GalTase activity. Anti-GalTase IgG, as well as the GalTase modifier protein, alpha-lactalbumin, both block GalTase activity and inhibited B16-F10 melanoma cell spreading on laminin, but not initial attachment. On the other hand, the addition of UDP galactose, which increases the catalytic turnover of GalTase, slightly increased cell spreading. None of these reagents had any effect on cell spreading on fibronectin. When GalTase substrates within laminin were either blocked by affinity-purified GalTase or eliminated by prior galactosylation, cell attachment appeared normal, but subsequent cell spreading was totally inhibited. The laminin substrate for GalTase was identified as N-linked oligosaccharides primarily on the A chain, and to a lesser extent on B chains. That N-linked oligosaccharides are necessary for cell spreading was shown by the inability of cells to spread on laminin surfaces pretreated with N-glycanase, even though cell attachment was normal. Cell surface GalTase was distinguished from other reported laminin binding proteins, most notably the 68-kD receptor, since they were differentially eluted from laminin affinity columns. These data show that surface GalTase does not participate during initial cell adhesion to laminin, but mediates subsequent cell spreading by binding to its appropriate N-linked oligosaccharide substrate. These results also emphasize that some of laminin's biological properties can be attributed to its oligosaccharide residues.

scholarly journals c-Abl phosphorylates Dok1 to promote filopodia during cell spreading

2004 ◽  
Vol 165 (4) ◽  
pp. 493-503 ◽  
Author(s):  
Pamela J. Woodring ◽  
Jill Meisenhelder ◽  
Sam A. Johnson ◽  
Guo-Lei Zhou ◽  
Jeffrey Field ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Tyrosine Kinase ◽  
Actin Cytoskeleton ◽  
Adaptor Protein ◽  
Cell Spreading ◽  
Unknown Mechanism ◽  
Abl Tyrosine Kinase ◽  
Src Homology 2 ◽  
Src Homology ◽  
Src Homology 2 Domain

Filopodia are dynamic F-actin structures that cells use to explore their environment. c-Abl tyrosine kinase promotes filopodia during cell spreading through an unknown mechanism that does not require Cdc42 activity. Using an unbiased approach, we identified Dok1 as a specific c-Abl substrate in spreading fibroblasts. When activated by cell adhesion, c-Abl phosphorylates Y361 of Dok1, promoting its association with the Src homology 2 domain (SH2)/SH3 adaptor protein Nck. Each signaling component was critical for filopodia formation during cell spreading, as evidenced by the finding that mouse fibroblasts lacking c-Abl, Dok1, or Nck had fewer filopodia than cells reexpressing the product of the disrupted gene. Dok1 and c-Abl stimulated filopodia in a mutually interdependent manner, indicating that they function in the same signaling pathway. Dok1 and c-Abl were both detected in filopodia of spreading cells, and therefore may act locally to modulate actin. Our data suggest a novel pathway by which c-Abl transduces signals to the actin cytoskeleton through phosphorylating Dok1 Y361 and recruiting Nck.

scholarly journals The Roles of Two Distinct Regions of PINCH-1 in the Regulation of Cell Attachment and Spreading

2010 ◽  
Vol 21 (23) ◽  
pp. 4120-4129 ◽  
Author(s):  
Satoko Ito ◽  
Yuko Takahara ◽  
Toshinori Hyodo ◽  
Hitoki Hasegawa ◽  
Eri Asano ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Focal Adhesion ◽  
Cell Attachment ◽  
Adaptor Protein ◽  
Cell Spreading ◽  
Terminal Region ◽  
The Other ◽  
Pivotal Role ◽  
Lim Domains ◽  
Integrin Linked Kinase

Cells attach to the extracellular matrix (ECM) through integrins to form focal adhesion complexes, and this process is followed by the extension of lamellipodia to enable cell spreading. PINCH-1, an adaptor protein essential for the regulation of cell–ECM adhesion, consists of five tandem LIM domains and a small C-terminal region. PINCH-1 is known to interact with integrin-linked kinase (ILK) and Ras suppressor protein 1 (Rsu-1); however, the precise mechanism by which this complex regulates cell–ECM adhesion is not fully understood. We report here that the LIM1 domain of PINCH-1, which associates with ILK to stabilize the expression of this protein, is sufficient for cell attachment but not for cell spreading. In contrast, the C-terminal region of PINCH-1, which binds to Rsu-1, plays a pivotal role in cell spreading but not in cell attachment. We also show that PINCH-1 associates with Rsu-1 to activate Rac1 and that Rac1 activation is necessary for cell spreading. Thus, these data reveal how specific domains of PINCH-1 direct two independent pathways: one utilizing ILK to allow cell attachment, and the other recruiting Rsu-1 to activate Rac1 in order to promote cell spreading.

Cardiac myocytes cultured on a basement membrane extract of the ehs tumor

1986 ◽  
Vol 44 ◽  
pp. 270-271
Author(s):  
L. Terracio ◽  
A. Dewey ◽  
K. Rubin ◽  
T.K. Borg
Keyword(s):  
Extracellular Matrix ◽  
Basement Membrane ◽  
Cardiac Myocytes ◽  
Normal Tissue ◽  
Cell Spreading ◽  
Collagen Iv ◽  
Basement Membrane Extract ◽  
Membrane Extract ◽  
Growth Development ◽  
Multicellular Organisms

The recognition and interaction of cells with the extracellular matrix (ECM) effects the normal physiology as well as the pathology of all multicellular organisms. These interactions have been shown to influence the growth, development, and maintenance of normal tissue function. In previous studies, we have shown that neonatal cardiac myocytes specifically interacts with a variety of ECM components including fibronectin, laminin, and collagens I, III and IV. Culturing neonatal myocytes on laminin and collagen IV induces an increased rate of both cell spreading and sarcomerogenesis.

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