Chick sensory neuronal growth cones distinguish fibronectin from laminin by making substratum contacts that resemble focal contacts

Gómez, Timothy M.; Roche, Florence K.; Letourneau, Paul C.

doi:10.1002/(sici)1097-4695(199601)29:1<18::aid-neu2>3.0.co;2-a

Cited by 86 publications

(51 citation statements)

References 66 publications

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“…The growth cones pull neurites forwards and are smaller than fibroblast lamellae. They distinguish FN from LN by forming contacts on FN similar to focal contacts in fibroblasts (Gomez et al, 1996). We speculate that stiff substrates support formation of focal contacts, which in turn stabilize interactions between growth cones and the matrix.…”

Section: Discussionmentioning

confidence: 79%

RPTPα is required for rigidity-dependent inhibition of extension and differentiation of hippocampal neurons

Kostić

Sap

Sheetz

2007

Journal of Cell Science

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Receptor-like protein tyrosine phosphatase α (RPTPα)-knockout mice have severe hippocampal abnormalities similar to knockouts of the Src family kinase Fyn. These enzymes are linked to the matrix-rigidity response in fibroblasts, but their function in neurons is unknown. The matrix-rigidity response of fibroblasts appears to differ from that of neuronal growth cones but it is unknown whether the rigidity detection mechanism or response pathway is altered. Here, we report that RPTPα is required for rigidity-dependent reinforcement of fibronectin (FN)-cytoskeleton bonds and the rigidity response in hippocampal neuron growth cones, like in fibroblasts. In control neurons, rigid FN surfaces inhibit neurite extension and neuron differentiation relative to soft surfaces. In RPTPα–/– neurons, no inhibition of extension and differentiation is found on both rigid and soft surfaces. The RPTPα-dependent rigidity response in neurons is FN-specific, and requires clustering of αvβ6 integrin at the leading edge of the growth cones. Further, RPTPα is necessary for the rigidity-dependent concentration of Fyn and p130Cas phosphorylation at the leading edge of the growth cone, like it is in fibroblasts. Although neurons respond to rigid FN surfaces in the opposite way to fibroblasts, we suggest that the mechanism of detecting FN rigidity is similar and involves rigidity-dependent RPTPα recruitment of Fyn.

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Section: Discussionmentioning

confidence: 79%

RPTPα is required for rigidity-dependent inhibition of extension and differentiation of hippocampal neurons

Kostić

Sap

Sheetz

2007

Journal of Cell Science

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“…Growth cone adhesion to the ECM is mediated by point contacts that are enriched in adhesion molecules such as ␤1-integrin, paxillin, vinculin, and zyxin (Gomez et al, 1996;Renaudin et al, 1999), but the mechanisms regulating point contact dynamics in growth cones are unknown. In this study, we define a Rho GTPase signaling cascade that regulates point contact assembly and stability.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, the Rho GTPases RhoA and RhoB are also enriched at point contacts. Point contacts exhibit different morphologies depending on substrata, suggesting functionally distinct adhesive sites may form in growth cones (Gomez et al, 1996). However, because growth cone point contacts are, on average, 10 times smaller and more punctate in appearance than fibroblastic focal adhesions, it is unclear whether these adhesion sites are regulated in a similar manner.…”

Section: Introductionmentioning

confidence: 99%

Rac1 and RhoA Promote Neurite Outgrowth through Formation and Stabilization of Growth Cone Point Contacts

2006

Self Cite

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Growth cone advance depends on coordinated membrane protrusion and adhesion to the extracellular matrix. Although many studies have addressed the mechanisms responsible for membrane protrusion, the assembly of integrin-dependent adhesion sites known as point contacts remains poorly understood in growth cones. We show balanced Rac1 activity controls both leading edge protrusion and point contact dynamics during neurite outgrowth. Immunocytochemistry and live imaging of paxillin-green fluorescent protein (GFP) showed that inhibiting Rac1 blocked point contact formation, whereas Rac1 overactivation produced small, unstable point contacts. Both inhibition and overactivation of Rac1 reduced the persistence of lamellar protrusions and neurite outgrowth. Inhibition of ROCK (Rho kinase), a RhoA effector, perturbed protrusion and point contact dynamics similar to Rac1 overactivation. Moreover, the repulsive guidance cue Semaphorin 3A, which signals through Rac1, destabilizes point contacts. Together, our data suggest that coordinated Rho GTPase activities regulate neurite outgrowth through point contact formation and stabilization of membrane protrusion.

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“…The corresponding rate of cell migration upon a surface depends on the simultaneous detachment and attachment to nearby ligands, causing extreme ligand densities (both high and low) to inhibit one of these two processes and subsequently limit cell migration rates. The outgrowth of neurites is analogous to cell migration (14), with receptor cluster morphology (15) and receptor dynamics at the growth cone (16) controlling the process.…”

mentioning

confidence: 99%

Three-dimensional Migration of Neurites Is Mediated by Adhesion Site Density and Affinity

Schense¹,

Hubbell²

2000

Journal of Biological Chemistry

147

111

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Three-dimensional neurite outgrowth rates within fibrin matrices that contained variable amounts of RGD peptides were shown to depend on adhesion site density and affinity. Bi-domain peptides with a factor XIIIa substrate in one domain and a RGD sequence in the other domain were covalently incorporated into fibrin gels during coagulation through the action of the transglutaminase factor XIIIa, and the RGD-dependent effect on neurite outgrowth was quantified, employing chick dorsal root ganglia cultured two-and three-dimensionally within the modified fibrin. Two separate bi-domain peptides were synthesized, one with a lower binding affinity linear RGD domain and another with a higher binding affinity cyclic RGD domain. Both peptides were crosslinked into fibrin gels at concentrations up to 8.2 mol of peptide/mol of fibrinogen, and their effect on neurite outgrowth was measured. Both two-and three-dimensional neurite outgrowth demonstrated a bi-phasic dependence on RGD concentration for both the linear and cyclic peptide, with intermediate adhesion site densities yielding maximal neurite extension and higher densities inhibiting outgrowth. The adhesion site density that yielded maximal outgrowth depended strongly on adhesion site affinity in both two and three dimensions, with lower densities of the higher affinity ligand being required (0.8 -1.7 mol/mol for the linear peptide versus 0.2 mol/mol for the cyclic peptide yielding maximum neurite outgrowth rates in three-dimensional cultures).Cell adhesion and migration in two and three dimensions play important roles in a host of physiological phenomena, including neurite extension (1), angiogenesis (2), and immune responses (3). The adhesion of cells within their environment is controlled primarily by the binding of cell surface receptors to short, exposed protein domains in the extracellular matrix. An important receptor family involved in adhesion and migration is the integrins, a class of heterodimeric receptors that interact with both extracellular matrix and cell-surface ligands (4, 5). Each unique dimeric receptor binds to a particular subset of ligands, which can often be mimicked with immobilized short peptides (6). One such short peptide that binds to integrins and influences subsequent cell adhesion and migration is RGD, a motif present in many proteins, including fibronectin, laminin, collagen, and fibrinogen (7). This sequence has been shown to be recognized by ␣ 5 ␤ 1 , ␣ v ␤ 3 (8), and several other integrin heterodimer pairs.Adhesion and migration upon a surface are distinct processes that depend on related molecular mechanisms. Cell adhesion involves the dynamic interaction between cell surface receptors and adhesion ligands on the supporting matrix (9, 10), with the strength of this attachment being related to the concentration of cell-surface receptors, the concentration of ligands available, and the specific binding affinity of the receptor ligands and pairs (11). Migration of cells upon a material is an analogous phenomenon, with the rate of cell...

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Chick sensory neuronal growth cones distinguish fibronectin from laminin by making substratum contacts that resemble focal contacts

Cited by 86 publications

References 66 publications

RPTPα is required for rigidity-dependent inhibition of extension and differentiation of hippocampal neurons

RPTPα is required for rigidity-dependent inhibition of extension and differentiation of hippocampal neurons

Rac1 and RhoA Promote Neurite Outgrowth through Formation and Stabilization of Growth Cone Point Contacts

Three-dimensional Migration of Neurites Is Mediated by Adhesion Site Density and Affinity

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