Thrombin causes neurite retraction in neuronal cells through activation of cell surface receptors

Suidan, Hana S.; Stone, Stuart R.; Hemmings, Brian A.; Monard, Denis

doi:10.1016/0896-6273(92)90302-t

Cited by 255 publications

(233 citation statements)

References 61 publications

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“…First, destabilization can be caused by the excessive local proteolytic degradation of components of the ECM as well as receptors for matrix molecules on the cell surface (e.g., Monard 1988). A second possible mechanism for destabilization of cell-substrate interaction could be effected by protease-mediated activation of a signal transduction pathway; for example, the activity of the protease thrombin causes the activation of cell surface receptors (Vu et al 1991), this being the apparent reason why thrombin causes neurite retraction in culture (Suidan et al 1992).…”

Section: Genes and Developmentmentioning

confidence: 99%

“…Proteases can modulate the interactions of the cell surface with the extracellular environment either directly, for example, by localized and directional degradation of the ECM (e.g., Pollanen et al 1988;Werb et al 1989), or indirectly by activating signal transduction pathways (Vu et al 1991) to effect, for example, the reorganization of cytoskeleton (Jalink and Moolenaar 19921 or neurite retraction (Suidan et al 1992). The enzymatic activities of most proteases are regulated, being synthesized as inactive zymogens that only become enzymatically active following processing.…”

Section: I(1)myospheroid (Rays)mentioning

confidence: 99%

“…Once activated, the domain of enzymatic activity can be further modulated by enzymatic inhibitors (see Hecht and Anderson 1992). The effects of the interplay of proteases (e.g., Gurwitz and Cunningham 1988;Dihanich et al 1991) and their inhibitors (Gloor et al 1986;Reinhard et al 1988) have been proposed to play an important role in growth cone motility and in neurite outgrowth (Monard 1988;Suidan et al 1992;Sumi et al 1992). Mutations in the Drosophila Stubble-stubbloid (Sb-sbd) gene, which encodes an apparent transmembrane protein with an extracellular serine protease domain, cause defects in cell shape and changes in the organization of microfilament bundles required for normal imaginal disc and bristle morphogenesis (Appel et al 1993).…”

Section: I(1)myospheroid (Rays)mentioning

confidence: 99%

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Masquerade: a novel secreted serine protease-like molecule is required for somatic muscle attachment in the Drosophila embryo.

Murugasu-Oei¹,

Rodrigues²,

Yang³

et al. 1995

Genes Dev.

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Diverse developmental processes, such as neuronal growth cone migration and cell shape changes, are mediated by the interactions of cells with the extracellular matrix. We describe here a secreted molecule encoded by the Drosophila masquerade (mas) gene. Total loss of mas function causes defective muscle attachment. This mutant phenotype suggests that mas normally acts to stabilize cell-matrix interaction and represents a novel functional and limiting component in the adhesion process, mas encodes a 1047-amino-acid preproprotein that is further processed by proteolytic cleavage to generate two polypeptides. The carboxy-terminal polypeptide is highly similar to serine proteases and has an extracellular localization; however, it is unlikely to possess proteolytic activity, because the catalytic site serine has been substituted by a glycine residue. During embryonic development, the mas amino-and carboxy-terminal polypeptides are differentially localized. The mas carboxy-terminal polypeptide accumulates at all somatic muscle attachment sites, which corresponds well with the morphological defect seen in the mas mutants. Our findings demonstrate the involvement of an extracellular component in somatic muscle attachment. We propose that mas acts via its modified serine protease motif, either as a novel adhesion molecule and/or as a competitive antagonist of serine proteases, to stabilize muscle attachment.

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Section: Genes and Developmentmentioning

confidence: 99%

Section: I(1)myospheroid (Rays)mentioning

confidence: 99%

Section: I(1)myospheroid (Rays)mentioning

confidence: 99%

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Masquerade: a novel secreted serine protease-like molecule is required for somatic muscle attachment in the Drosophila embryo.

Murugasu-Oei¹,

Rodrigues²,

Yang³

et al. 1995

Genes Dev.

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“…3 indicate that proteolysis of PAR-l in the Ad12 HER 10 cells is extremely rapid, with the vast majority of receptors cleaved within 2 mm. Thrombin-induced changes in neural cell morphology are also extremely rapid, having been measured at optimal thrombin concentrations over a range from 10 s to 3 mm (Jalink and Mootenaar, 1992;Suidan et al, 1992). Proteolytic activation of PAR-I has been the inferred mechanism for neurite retraction based on analogy to other thrombin/PAR-I signaling systems and previous findings that PAR-I activating peptides can induce the effect (Jalirik and Mootenaar, 1992;Suidan et al, 1992).…”

Section: Par-i Cell Surface Expression May Allow For Both Normal Devementioning

confidence: 99%

“…Additionally, PAR-I's existence at the neural cell surface has been inferred for some time based on morphologic, physiologic, and biochemical responses to both thrombin and PAR-I activating peptides (Jatink and Moolenaar, 1992;Suidan et al, 1992;Beecher et al, 1994;Grabham and Cunningham, 1995;Smith-Swintosky et al, 1995;Vaughan et at., 1995;Yang et al, 1997). In the present study, PAR-I cell surface expression is directly demonstrated and quantitated in a human neural cell line (Ad12 HER 10).…”

Section: Par-i Cell Surface Expression May Allow For Both Normal Devementioning

confidence: 99%

Injury‐Related Factors and Conditions Down‐Regulate the Thrombin Receptor (PAR‐1) in a Human Neuronal Cell Line

Weinstein

Lau

Brass

et al. 1998

Journal of Neurochemistry

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Jou,uif ot NCUrO('/U'iniStJ'rAbstract: Previous studies have demonstrated that thrombin can induce potent effects on neural cell morphology, biochemistry, and viability. Nearly all of these effects are mediated by proteolytic activation of the thrombin receptor (PAR-i). Mechanisms of PAR-i regulation in several nonneural cell types have been shown to be novel and cell type specific; however, little is known about PAR-i regulation in neural cells. In the present study, PAR-i cell surface expression and regulation were examined in a transformed retinoblast (Adi 2 HER i 0) cell line using radioiodinated anti-PAR-i monoclonal antibodies ATAP2, which recognizes intact and cleaved receptors, and SPANi2, which is specific for the intact form of the receptor. Scatchard analysis revealed high-affinity, specific binding to a single affinity class of receptors: K= 3.13 and 5.25 nM, Bmax = i90.i and 67.8 fmol/mg of protein for 1251-ATAP2 and 125l-SPANi2, respectively. Specificity for PAR-i was confirmed by demonstrating rapid and near complete decreases for both antibodies following treatment with thrombin or PAR-i activating peptide (SFLLRN). Differential antibody binding was used to demonstrate rapid and near complete thrombininduced PAR-i cleavage and internalization, with protein synthesis-dependent replacement of intact receptors occurring over longer time intervals, but only minimal recycling of cleaved receptors. A variety of factors and conditions were screened for their effects on PAR-i expression. Significant decreases in PAR-i expression were induced by the protein kinase C activator phorbol 12-myristate i3-acetate (87% at 3 h), the phospholipid inflammatory mediator lysophosphatidic acid (32% at 3 h), and the injury-related condition hypoglycemia (64 and 100% at 24 h in the absence and presence of dibutyryl cyclic AMP, respectively). The effect of hypoglycemia was shown by RNase protection to be at least partially pretranslational. Finally, thrombin's ability to enhance hypoglycemia-induced cell killing correlated temporally with PAR-i cell surface expression. Key Words: Thrombin receptor-PAR-i -Regulation-Neurons-Lysophosphatidic acid-Hypoglycemia-Antibody. J. Neurochem. 71, i034-i050 (i998).Over the last decade, evidence has accumulated implicating the multifunctional serine protease thrombin in a variety of developmental, physiologic, and pathophysiologic functions in the nervous system (for review, see Grand et al., 1996). Thrombin can induce a variety of effects on cultured neural cells, including neurite retraction (Gurwitz and Cunningham, 1988; Grand et al., 1989;Farmer et al., 1990), reversal of astrocyte stellation (Cavanaugh et al

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Distinct effects of recombinant tenascin-C domains on neuronal cell adhesion, growth cone guidance, and neuronal polarity

et al. 1996

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Using a set of recombinantly expressed proteins, distinct domains of the mouse extracellular matrix glycoprotein tenascin‐C, hereafter called tenascin, have been identified to confer adhesion, anti‐adhesion, and changes in morphology of neuronal cells. In short‐term adhesion assays (1 hr), cerebellar and hippocampal neurons adhered to several domains, encompassing the fibronectin type III‐like (FN III) repeats 1–2 and 6–8, as well as to the alternatively spliced FN III repeats and to tenascin itself. Although no short‐term adhesion to the EGF repeats containing fragment could be detected under the conditions used, it was anti‐adhesive for neuronal cell bodies and repellent for growth cone advance and neuritogenesis. FN III repeats 3–5 were repellent only for growth cones but not for neuronal cell bodies. Neurite outgrowth promoting activities at early stages and induction of a polarized neuronal morphology at later stages of differentiation were associated with the EGF repeats and the FN III repeats 6–8. These observations suggest differential effects of particular domains of the tenascin molecule on distinct cellular compartments, i.e., cell body, axon and dendrite, and existence of multiple neuronal receptors with distinct intracellular signaling features. © 1996 Wiley‐Liss, Inc.

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Thrombin causes neurite retraction in neuronal cells through activation of cell surface receptors

Cited by 255 publications

References 61 publications

Masquerade: a novel secreted serine protease-like molecule is required for somatic muscle attachment in the Drosophila embryo.

Masquerade: a novel secreted serine protease-like molecule is required for somatic muscle attachment in the Drosophila embryo.

Injury‐Related Factors and Conditions Down‐Regulate the Thrombin Receptor (PAR‐1) in a Human Neuronal Cell Line

Distinct effects of recombinant tenascin-C domains on neuronal cell adhesion, growth cone guidance, and neuronal polarity

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