Beta 1 integrins signal lipid second messengers required during cell adhesion.

Auer, Kelly L.; Jacobson, Bernard

doi:10.1091/mbc.6.10.1305

Cited by 51 publications

(50 citation statements)

References 63 publications

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“…Interestingly, in HeLa cells LOX metabolism of AA signaled spreading; however, AA release continued even after spreading was complete (Auer and Jacobson, 1995). A similarly sustained AA release after spreading in initial assays was noted in NIH-3T3 cells as well.…”

Section: Introductionmentioning

confidence: 74%

“…It remained to be explained why the decrease in ERK1/2-mediated PLA2 activity seen by others did not affect spreading in NIH-3T3 cells, although AA release was required for spreading. We proposed to test whether a kinetic or mass effect of AA release regulated by ERK1/2 is involved in signaling cell spreading or a later stage of adhesion, and what relationship this might have to a potential induction of COX-2 expression.Interestingly, in HeLa cells LOX metabolism of AA signaled spreading; however, AA release continued even after spreading was complete (Auer and Jacobson, 1995). A similarly sustained AA release after spreading in initial assays was noted in NIH-3T3 cells as well.…”

mentioning

confidence: 74%

“…An equivalent amount of fresh medium was added back to the plates to maintain the original plated volume. AA release was evaluated as appearance of label in the medium supernatant; under these conditions AA is the predominant labeled product released into medium for ϳ60 min (Auer and Jacobson, 1995;Lloret and Moreno, 1996;Muthalif et al, 1998). Sample cpm was averaged per time point and presented as a percentage of the counts in the preplating medium at the beginning of the experiment.…”

Section: Arachidonic Acid Release Assaysmentioning

confidence: 99%

“…© 2001 by The American Society for Cell Biology 1937 a lipoxygenase (LOX), but not by cyclooxygenases (COXs), was required for subsequent activation of protein kinase C to enable cell spreading Jacobson, 1992, 1993;Auer and Jacobson, 1995). PLA2-mediated AA release was also shown to be a requirement for ␤1-integrin-mediated NIH-3T3 cell spreading on a fibronectin (FN) matrix (Whitfield and Jacobson, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…In addition to showing that the cell spreading and migration stages are sequentially regulated and modulated by the divergence of LOX and COX branches of AA oxidation, we show that migration is also influenced at the level of gene transcription by the induction of COX-2 synthesis. The above-mentioned conclusions are schematically presented in Figure 11, and the discussion of the results that led to them is given below.Although the spreading stage of NIH-3T3 cells on fibronectin, as with that of HeLa cells on a collagen substrate, uses an AA signaling pathway summarized by PLA2 3 AA 3 LOX 3 LT (Figures 1-3; Jacobson, 1992, 1993;Auer and Jacobson, 1995;Chun et al, 1996Chun et al, , 1997Crawford and Jacobson, 1998;Whitfield and Jacobson, 1999), less is known of whether other oxidative enzymes of AA are involved. Roles for both the LOX and COX branches of AA metabolism have been implicated in growth factor-induced cytoskeletal changes such as stress fiber breakdown (Peppelenbosch et al, 1992) but how this impacts cell adhesion is not known.…”

mentioning

confidence: 99%

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Modulation of Cell-Substrate Adhesion by Arachidonic Acid: Lipoxygenase Regulates Cell Spreading and ERK1/2-inducible Cyclooxygenase Regulates Cell Migration in NIH-3T3 Fibroblasts

Stockton

Jacobson

2001

MBoC

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Adhesion of cells to an extracellular matrix is characterized by several discrete morphological and functional stages beginning with cell-substrate attachment, followed by cell spreading, migration, and immobilization. We find that although arachidonic acid release is rate-limiting in the overall process of adhesion, its oxidation by lipoxygenase and cyclooxygenases regulates, respectively, the cell spreading and cell migration stages. During the adhesion of NIH-3T3 cells to fibronectin, two functionally and kinetically distinct phases of arachidonic acid release take place. An initial transient arachidonate release occurs during cell attachment to fibronectin, and is sufficient to signal the cell spreading stage after its oxidation by 5-lipoxygenase to leukotrienes. A later sustained arachidonate release occurs during and after spreading, and signals the subsequent migration stage through its oxidation to prostaglandins by newly synthesized cyclooxygenase-2. In signaling migration, constitutively expressed cyclooxygenase-1 appears to contribute ϳ25% of prostaglandins synthesized compared with the inducible cyclooxygenase-2. Both the second sustained arachidonate release, and cyclooxygenase-2 protein induction and synthesis, appear to be regulated by the mitogen-activated protein kinase extracellular signal-regulated kinase (ERK)1/2. The initial cell attachment-induced transient arachidonic acid release that signals spreading through lipoxygenase oxidation is not sensitive to ERK1/2 inhibition by PD98059, whereas PD98059 produces both a reduction in the larger second arachidonate release and a blockade of induced cyclooxygenase-2 protein expression with concomitant reduction of prostaglandin synthesis. The second arachidonate release, and cyclooxygenase-2 expression and activity, both appear to be required for cell migration but not for the preceding stages of attachment and spreading. These data suggest a bifurcation in the arachidonic acid adhesion-signaling pathway, wherein lipoxygenase oxidation generates leukotriene metabolites regulating the spreading stage of cell adhesion, whereas ERK 1/2-induced cyclooxygenase synthesis results in oxidation of a later release, generating prostaglandin metabolites regulating the later migration stage. INTRODUCTIONCell adhesion to the extracellular matrix (ECM) is a sequential process of discrete temporal stages. Detached cells, e.g., leukocytes, metastasized cancer cells, or suspension-cultured cells, initially attach to an ECM protein substrate by means of plasma membrane receptors. Attached cells then undergo spreading, which results in flattening and the formation of focal adhesions. Subsequently, some cell types undergo migration on the ECM, whereas others remain stationary. Each of these stages of adhesion, i.e., attachment, spreading, migration, and immobilization, involves changes in morphology and cytoskeletal structure that are regulated by incompletely defined protein kinase and lipid second messenger pathways (reviewed in Huttenlocher et al., 1995;Heidemann an...

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Section: Introductionmentioning

confidence: 74%

mentioning

confidence: 74%

Section: Arachidonic Acid Release Assaysmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Modulation of Cell-Substrate Adhesion by Arachidonic Acid: Lipoxygenase Regulates Cell Spreading and ERK1/2-inducible Cyclooxygenase Regulates Cell Migration in NIH-3T3 Fibroblasts

Stockton

Jacobson

2001

MBoC

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Arachidonate initiated protein kinase C activation regulates HeLa cell spreading on a gelatin substrate by inducing F-actin formation and exocytotic upregulation of β1 Integrin

1997

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HeLa cell spreading on a gelatin substrate requires the activation of protein kinase C (PKC), which occurs as a result of cell-attachment-induced activation of phospholipase A2 (PLA2) to produce arachidonic acid (AA) and metabolism of AA by lipoxyginase (LOX). The present study examines how PKC activation affects the actin- and microtubule-based cytoskeletal machinery to facilitate HeLa cell spreading on gelatin. Cell spreading on gelatin is contingent on PKC induction of both actin polymerization and microtubule-facilitated exocytosis, which is based on the following observations. There is an increase in the relative content of filamentous (F)-actin during HeLa cell spreading, and treating HeLa cells with PKC-activating phorbol esters such as 12-O-tetradecanoyl phorbol 13-acetate (TPA) further increases the relative content of F-actin and the rate and extent to which the cells spread. Conversely, inhibition of PKC by calphostin C blocked both cell spreading and the increase of F-actin content. The increased F-actin content induced by PKC activators also was observed in suspension cells treated with TPA, and the kinetics of F-actin were similar to that for PKC activation. In addition, PKC epsilon, which is the PKC isoform most involved in regulating HeLa cell spreading in response to AA production, is more rapidly translocated to the membrane in response to TPA treatment than is the increase in F-actin. Blocking the activities of either PLA2 or LOX inhibited F-actin formation and cell spreading, both of which were reversed by TPA treatment. This result is consistent with AA and a LOX metabolite of AA as being upstream second messengers of activation of PKC and its regulation of F-actin formation and cell spreading. PKC appears to activate actin polymerization in the entire body of the cell and not just in the region of cell-substrate adhesion because activated PKC was associated not only with the basolateral plasma membrane domain contacting the culture dish but also with the apical plasma membrane domain exposed to the culture medium and with an intracellular membrane fraction. In addition to the facilitation of F-actin formation, activation of PKC induces the exocytotic upregulation of beta 1 integrins from an intracellular domain to the cell surface, possibly in a microtubule-dependent manner because the upregulation is inhibited by Nocodazole. The results support the concept that cell-attachment-induced AA production and its metabolism by LOX results in the activation of PKC, which has a dual role in regulating the cytoskeletal machinery during HeLa cell spreading. One is through the formation of F-actin that induces the structural reorganization of the cells from round to spread, and the other is the exocytotic upregulation of collagen receptors to the cell surface to enhance cell spreading.

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Role for cell adhesion and glycosyl (HNK-1 and oligomannoside) recognition in the sharpening of the regenerating retinotectal projection in goldfish

Schmidt¹,

Schachner²

1998

J. Neurobiol.

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Cell‐adhesion molecules (CAMs) are thought to play crucial roles in development and plasticity in the nervous system. This study tested for a role for cell adhesion and in particular, the recognition of two glycosyl epitopes (HNK‐1 and oligomannoside) in the activity‐driven sharpening of the retinotopic map formed by the regenerating retinal fibers of goldfish. HNK‐1 is a prominent glycosyl epitope on many CAMs and extracellular matrix (ECM) molecules, including NCAM, L1, ependymin, and integrins, which have all been implicated in synaptic plasticity. To test for a role of HNK‐1 in the sharpening process, we used osmotic minipumps to infuse HNK‐1 antibodies for 7–21 days into the tectal ventricle starting at 18 days after optic nerve crush. Retinotopic maps recorded at 76–86 days postcrush showed a lack of sharpening similar to that seen previously with two antibodies to ependymin, an HNK‐1–positive ECM component present in cerebrospinal fluid. The multiunit receptive fields at each point averaged 26° versus 11–12° in regenerates infused with control antibodies or Ringer's alone. The HNK‐1 epitope also binds to the G2 domain of laminin to mediate neuron‐ECM adhesion. To test for a role for laminin, a polyclonal antibody was similarly infused and also prevented sharpening to approximately the same degree. The results support a role for the HNK‐1 epitope and laminin in retinotectal sharpening. The oligomannoside epitope (recognized by monoclonal antibody L3) on the CAM L1 interacts with NCAM on the same cell to promote stronger L1 homophilic interactions between cells. Both an L1‐like molecule and NCAM are prominently reexpressed in the regenerating retinotectal system of fish. Infusion of oligomannosidic glycopeptides resulted in decreased sharpening, with multiunit receptive fields that averaged 22.7°. Infusions of mannose‐poor glycopeptides less prominently disrupted sharpening, with average multiunit receptive fields of 18°. Thus, oligomannosidic glycans in particular may play a role in retinotopic sharpening. Blocking glycan‐mediated interactions between CAMs and ECM molecules could decrease the extent of exploratory growth of retinal axon collaterals, preventing them from finding their retinotopic sites, or could interfere with L1 or NCAM and laminin binding at the synaptic densities preventing stabilization of retinotopically appropriate synapses. Together, these results support a prominent role for cell adhesion and glycan epitopes in visual synaptic plasticity. © 1998 John Wiley & Sons, Inc. J Neurobiol 37: 659–671, 1998

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Beta 1 integrins signal lipid second messengers required during cell adhesion.

Cited by 51 publications

References 63 publications

Modulation of Cell-Substrate Adhesion by Arachidonic Acid: Lipoxygenase Regulates Cell Spreading and ERK1/2-inducible Cyclooxygenase Regulates Cell Migration in NIH-3T3 Fibroblasts

Modulation of Cell-Substrate Adhesion by Arachidonic Acid: Lipoxygenase Regulates Cell Spreading and ERK1/2-inducible Cyclooxygenase Regulates Cell Migration in NIH-3T3 Fibroblasts

Arachidonate initiated protein kinase C activation regulates HeLa cell spreading on a gelatin substrate by inducing F-actin formation and exocytotic upregulation of β1 Integrin

Role for cell adhesion and glycosyl (HNK-1 and oligomannoside) recognition in the sharpening of the regenerating retinotectal projection in goldfish

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