Neuronal extracellular proteases facilitate cell migration, axonal growth, and pathfinding

Seeds, Nicholas W.; Siconolfi, Lisa B.; Haffke, Susan

doi:10.1007/978-3-642-60905-3_23

Cited by 10 publications

(13 citation statements)

References 37 publications

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“…1996; Parmer et al. 1997) and that plasminogen activators play an active role in growth cone movement (Seeds et al. 1997), the effect of PACAP on tPA secretion in CGN‐conditioned medium was investigated by zymography assay.…”

Section: Resultsmentioning

confidence: 99%

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Pituitary adenylate cyclase‐activating polypeptide (PACAP) stimulates the expression and the release of tissue plasminogen activator (tPA) in neuronal cells: involvement of tPA in the neuroprotective effect of PACAP

Raoult¹,

Roussel²,

Bénard³

et al. 2011

Journal of Neurochemistry

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Pituitary adenylate cyclase-activating polypeptide (PACAP) and tissue plasminogen activator (tPA) play important roles in neuronal migration and survival. However, a direct link between the neurotrophic effects of PACAP and tPA has never been investigated. In this study, we show that, in PC12 cells, PACAP induced a 9.85-fold increase in tPA gene expression through activation of the protein kinase A-and protein kinase C-dependent signaling pathways. In immature cerebellar granule neurons (CGN), PACAP stimulated tPA mRNA expression and release of proteolytically active tPA. Immunocytochemical labeling revealed the presence of tPA in the cytoplasm and processes of cultured CGN. The inhibitory effect of PACAP on CGN motility was not affected by the tPA substrate plasminogen or the tPA inhibitor plasminogen activator inhibitor-1. In contrast, plasminogen activator inhibitor-1 significantly reduced the stimulatory effect of PACAP on CGN survival. Altogether, these data indicate that tPA gene expression is activated by PACAP in both tumoral and normal neuronal cells. The present study also demonstrates that PACAP stimulates the release of tPA which promotes CGN survival by a mechanism dependent of its proteolytic activity.

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Section: Resultsmentioning

confidence: 99%

“…2002). Interestingly, during cerebellum development, tPA is concentrated in leading processes of granule cells (CGN) (Krystosek and Seeds 1981a,b; Seeds et al. 1997) where it facilitates CGN migration (Seeds et al.…”

mentioning

confidence: 99%

Pituitary adenylate cyclase‐activating polypeptide (PACAP) stimulates the expression and the release of tissue plasminogen activator (tPA) in neuronal cells: involvement of tPA in the neuroprotective effect of PACAP

Raoult¹,

Roussel²,

Bénard³

et al. 2011

Journal of Neurochemistry

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“…Second, tPA and uPA have an extremely narrow substrate specificity, and have been shown to act directly upon only a handful of proteins (notably plasminogen and hepatocyte growth factor); in these cases, they activate functional states of the proteins. Third, like reelin, plasminogen activator has been strongly implicated in regulating neuronal migration [1,2,25], synaptic plasticity [3,4,26] and long-term potentiation [27,28]. Further studies are needed to test the hypothesis that processing of reelin by tPA or uPA "activates" some of its in vivo functions, and that some of the effects of plasminogen activators on neural development and function may be mediated via reelin.…”

Section: Discussionmentioning

confidence: 99%

Methodological factors influencing measurement and processing of plasma reelin in humans

et al. 2003

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BackgroundReelin, intensively studied as an extracellular protein that regulates brain development, is also expressed in a variety of tissues and a circulating pool of reelin exists in adult mammals. Here we describe the methodological and biological foundation for carrying out and interpreting clinical studies of plasma reelin.ResultsReelin in human plasma was sensitive to proteolysis, freeze-thawing and heating during long-term storage, sample preparation and electrophoresis. Reelin in plasma was a dimer under denaturing conditions. Boiling of samples resulted in laddering, suggesting that each of the 8 repeats expressed in reelin contains a heat-labile covalent bond susceptible to breakage. Urinary-type and tissue-type plasminogen activator converted reelin to a discrete 310 kDa fragment co-migrating with the major immunoreactive reelin fragment seen in plasma and also detected in brain. (In contrast, plasmin produced a spectrum of smaller unstable reelin fragments.) We examined archival plasma of 10 pairs of age-matched male individuals differing in repeat length of a CGG repeat polymorphism of the 5'-untranslated region of the reelin gene (both alleles < 11 repeats vs. one allele having >11 repeats). Reelin 310 kDa band content was lower in subjects having the long repeats in all 10 pairs, by 25% on average (p < 0.001). In contrast, no difference was noted for amyloid precursor protein.ConclusionsOur studies indicate the need for caution in measuring reelin in archival blood samples, and suggest that assays of plasma reelin should take into account three dimensions that might vary independently: a) the total amount of reelin protein; b) the relative amounts of reelin vs. its proteolytic processing products; and c) the aggregation state of the native protein. Reelin-plasminogen activator interactions may affect their roles in synaptic plasticity. Our results also suggest that the human CGG repeat polymorphism affects reelin gene expression, and may affect susceptibility to human disease.

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“…2e) although axons are known to release proteolytic enzymes during their growth (Krystosek and Seeds 1981;Seeds et al 1997;Webber et al 2002;Pizzi and Crowe 2007). This might be due to the specificity of antibody detection, i.e., polypeptides bearing epitopes recognised by the polyclonal anti-streptavidin antibody remained on the substrate even after their partial degradation.…”

Section: Technical Advantages Of Using the Streptavidin-biotin-csd Comentioning

confidence: 97%

Influences of retinal axons on the cultural substrate containing biotin-conjugated chondroitin sulfate in vitro

et al. 2010

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Although chondroitin sulfate (CS) is known to act as an inhibitory axon guidance cue, retinal axons show substantial growth on a culture substrate containing CS. Thus, the question arises as to how retinal axons elongate on CS-containing culture substrates. To elucidate the effects of retinal axons on a substrate containing CS, we synthesized biotinylated CS (biotin-CS) and developed a culture substrate with streptavidin-conjugated biotin-CS (complex between streptavidin and biotin-CS) to culture retinal axons. The effects of retinal axons on the streptavidin-biotin-CS complex were analyzed immunocytochemically using antibodies against CS and streptavidin, which recognize the carbohydrate and protein portions of the complex, respectively. After the axons were cultured on the substrate, areas that were CS-immunonegative but streptavidin-immunopositive were observed on the surface, corresponding to areas with or without axons, respectively. Absence of CS immunostaining was considered to be caused by structural alterations in the carbohydrate chains of the CS under the influence of the axons.

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Neuronal extracellular proteases facilitate cell migration, axonal growth, and pathfinding

Cited by 10 publications

References 37 publications

Pituitary adenylate cyclase‐activating polypeptide (PACAP) stimulates the expression and the release of tissue plasminogen activator (tPA) in neuronal cells: involvement of tPA in the neuroprotective effect of PACAP

Pituitary adenylate cyclase‐activating polypeptide (PACAP) stimulates the expression and the release of tissue plasminogen activator (tPA) in neuronal cells: involvement of tPA in the neuroprotective effect of PACAP

Methodological factors influencing measurement and processing of plasma reelin in humans

Influences of retinal axons on the cultural substrate containing biotin-conjugated chondroitin sulfate in vitro

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