Neuronal plasminogen activators: cell surface binding sites and involvement in neurite outgrowth

Pittman, Randall N.; Ivins, Jonathan K.; Buettner, Helen M.

doi:10.1523/jneurosci.09-12-04269.1989

Cited by 208 publications

(156 citation statements)

References 69 publications

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“…1, available at www.jneurosci.org as supplemental material). Expression of binding sites for plasminogen (Parmer et al, 2000;Miles et al, 2002) and t-PA (Pittman et al, 1989;Parmer et al, 2000), together with the demonstration of trafficking of t-PA to catecholamine storage vesicles (Parmer et al, 1997;Parmer and Miles, 1998), suggests the presence of a local catecholaminergic cell plasminogen/t-PA system that regulates cell-associated neuroendocrine prohormone processing that, in turn, may play a key role in the regulation of neurotransmitter release. Of note, molecules of the plasminogen activation pathway are present in a variety of neuroendocrine sites, including the cerebral cortex (Sappino et al, 1993), cerebellum (Sappino et al, 1993;Friedman and Seeds, 1995 (Parmer et al, 1997;Zhang et al, 2002), and in peripheral sympathetic neurons (X.…”

Section: Discussionmentioning

confidence: 99%

“…PC12 cells synthesize and release t-PA in response to secretagogue stimulation (Gualandris et al, 1996;Parmer et al, 1997). Furthermore, the plasminogen activator urokinase and its receptor uPAR are present in these cells (Pittman et al, 1989;Fowler et al, 1998;Herschman et al, 2000). Therefore, we tested whether endogenous cellular plasminogen activators could contribute to the cell-dependent plasminogen activation.…”

Section: Cellular Augmentation Of Plasminogen Activation On Catecholamentioning

confidence: 99%

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Cell-Surface Actin Binds Plasminogen and Modulates Neurotransmitter Release from Catecholaminergic Cells

Miles¹,

Andronicos²,

Baik³

et al. 2006

J. Neurosci.

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An emerging area of research has documented a novel role for the plasminogen activation system in the regulation of neurotransmitter release. Prohormones, secreted by cells within the sympathoadrenal system, are processed by plasmin to bioactive peptides that feed back to inhibit secretagogue-stimulated release. Catecholaminergic cells of the sympathoadrenal system are prototypic prohormone-secreting cells. Processing of prohormones by plasmin is enhanced in the presence of catecholaminergic cells, and the enhancement requires binding of plasmin(ogen) to cellular receptors. Consequently, modulation of the local cellular fibrinolytic system of catecholaminergic cells results in substantial changes in catecholamine release. However, mechanisms for enhancing prohormone processing and cellsurface molecules mediating the enhancement on catecholaminergic cells have not been investigated. Here we show that plasminogen activation was enhanced Ͼ6.5-fold on catecholaminergic cells. Carboxypeptidase B treatment decreased cell-dependent plasminogen activation by ϳ90%, suggesting that the binding of plasminogen to proteins exposing C-terminal lysines on the cell surface is required to promote plasminogen activation. We identified catecholaminergic plasminogen receptors required for enhancing plasminogen activation, using a novel strategy combining targeted specific proteolysis using carboxypeptidase B with a proteomics approach using twodimensional gel electrophoresis, radioligand blotting, and tandem mass spectrometry. Two major plasminogen-binding proteins that exposed C-terminal lysines on the cell surface contained amino acid sequences corresponding to ␤/␥-actin. An anti-actin monoclonal antibody inhibited cell-dependent plasminogen activation and also enhanced nicotine-dependent catecholamine release. Our results suggest that cell-surface-expressed forms of actin bind plasminogen, thereby promoting plasminogen activation and increased prohormone processing leading to inhibition of neurotransmitter release.

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Section: Discussionmentioning

confidence: 99%

Section: Cellular Augmentation Of Plasminogen Activation On Catecholamentioning

confidence: 99%

Cell-Surface Actin Binds Plasminogen and Modulates Neurotransmitter Release from Catecholaminergic Cells

Miles¹,

Andronicos²,

Baik³

et al. 2006

J. Neurosci.

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“…The plasminogen activators are secreted proteases that bind cell surfaces to localize proteolytic activity to cell-cell and cellsubstratum sites (Vassalli et al, 1985;Ichinose et al, 1986;Knudsen et al, 1986;Plow et al, 1986;Pollanen et al, 1988;Verrall andSeeds, 1988, 1989;Pittman et al, 1989). uPA binds to a well characterized receptor (uPAR) on cell surfaces (Estreicher et al, 1989), and this binding enhances uPA activity (Vassalli et al, 1985).…”

Section: Abstract: Nerve Regeneration; Sensory Neurons; Tissue Plasmmentioning

confidence: 99%

Induction of the Plasminogen Activator System Accompanies Peripheral Nerve Regeneration after Sciatic Nerve Crush

Siconolfi

Seeds

2001

J. Neurosci.

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Peripheral nerve regeneration is dependent on the ability of regenerating neurites to migrate through cellular debris and altered extracellular matrix at the injury site, grow along the residual distal nerve sheath conduit, and reinnervate synaptic targets. In cell culture, growth cones of regenerating axons secrete proteases, specifically plasminogen activators (PAs), which are believed to facilitate growth cone movement by digesting extracellular matrices and cell adhesions. In this study, the PA system was shown to be specifically activated in sensory neurons after sciatic nerve crush in adult mice. The number of sensory neurons expressing urokinase PA receptor (uPAR) mRNA levels increased above sham levels by 8 hr after crush, whereas the number of sensory neurons expressing uPA and tissue PA (tPA) mRNAs was significantly increased by 3 d after crush. PA mRNA levels were also increased at the crush site, with uPA mRNA elevated by 8 hr after crush and tPA and uPAR mRNA levels markedly increased by 7 d. PA-dependent enzymatic activity was significantly increased from 1 to 7 d after crush in nerves that had been crushed compared with uncrushed nerves. Immunohistochemistry showed that tPA was localized within regenerating axons of the sciatic nerve. There were no significant changes in plasminogen activator inhibitor 1 activity between crush and sham after the injury. These results clearly demonstrated that after injury the PA system was rapidly induced in sensory neurons, where it may play an important role in nerve regeneration in vivo.

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“…Within the developing nervous system, the expression of t-PA and u-PA is restricted to migrating tissues such as cerebellar granule cells (11) and neural crest cells (6) and to regions of axonal growth such as the floor plate of the spinal cord (6,8). Plg activators are also found on the neurites of differentiating rat sympathetic neurons (12), neuroblastoma cells (7), and PC-12 cells (13).…”

mentioning

confidence: 99%

Neuritogenesis and the Nerve Growth Factor-induced Differentiation of PC-12 Cells Requires Annexin II-mediated Plasmin Generation

Jacovina¹,

Zhong

Khazanova

et al. 2001

Journal of Biological Chemistry

108

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One of the key morphological changes associated with the nerve growth factor (NGF)-induced differentiation of rat adrenal pheochromocytoma (PC-12) cells is the growth of axon-like processes called neurites. A growing body of evidence suggests that this process may be dependent upon plasmin, a serine protease generated from plasminogen (Plg) by either urokinase Plg activator (u-PA) or tissue Plg activator (t-PA). Prior work in our laboratory has identified annexin II (Ann-II) as a coreceptor for Plg and t-PA that promotes and localizes plasmin generation near the cell surface. In the present study, we report a 3-9-fold increase in Ann-II protein and message levels in NGF-treated PC-12 cells. Message stability and nuclear run-on assays suggest that this induction occurs at the level of gene transcription. Neurite outgrowth assays on and within a three-dimensional matrix demonstrate the inhibition of NGF-induced PC-12 cell differentiation by polyclonal and monoclonal antibodies directed against Ann-II as well as by the overexpression of antisense Ann-II mRNA. Neuritogenesis is also impaired by ␣ 2 -plasmin inhibitor, antibodies directed against t-PA and u-PA, and ⑀-aminocaproic acid, a lysine analog that inhibits Plg activation and the binding of Plg to Ann-II. Plasmin generation assays reveal a 2-fold increase in plasmin production on NGF-treated PC-12 cells, which can be blocked by a polyclonal antibody directed against the tail region of Ann-II. From these data, we conclude that Ann-II is transcriptionally up-regulated by NGF and that Ann-II-mediated plasmin generation may play an important role during neurite development in the differentiating PC-12 cell.

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Neuronal plasminogen activators: cell surface binding sites and involvement in neurite outgrowth

Cited by 208 publications

References 69 publications

Cell-Surface Actin Binds Plasminogen and Modulates Neurotransmitter Release from Catecholaminergic Cells

Cell-Surface Actin Binds Plasminogen and Modulates Neurotransmitter Release from Catecholaminergic Cells

Induction of the Plasminogen Activator System Accompanies Peripheral Nerve Regeneration after Sciatic Nerve Crush

Neuritogenesis and the Nerve Growth Factor-induced Differentiation of PC-12 Cells Requires Annexin II-mediated Plasmin Generation

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