Heparan sulfate proteoglycans: structure, protein interactions and cell signaling

Dreyfuss, Juliana Luporini; Regatieri, Caio V.; Jarrouge, Thais R.; Cavalheiro, Renan P.; Sampaio, Lúcia O.; Nader, Helena B.

doi:10.1590/s0001-37652009000300007

Cited by 209 publications

(165 citation statements)

References 212 publications

(96 reference statements)

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“…Similar to the endocytosis pathway for a variety of extracellular ligands, we found angiogenin uptake to be consistent with heparan sulfate proteoglycan-assisted CME (Belting, 2003;Dreyfuss et al, 2009). It has been shown previously that angiogenin binds heparin and cell surface proteoglycans (Soncin et al, 1994(Soncin et al, , 1997.…”

Section: Discussionsupporting

confidence: 85%

Motoneurons Secrete Angiogenin to Induce RNA Cleavage in Astroglia

Skorupa

King²,

Aparicio³

et al. 2012

J. Neurosci.

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Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder affecting motoneurons. Mutations in angiogenin, encoding a member of the pancreatic RNase A superfamily, segregate with ALS. We previously demonstrated that angiogenin administration shows promise as a neuroprotective therapeutic in studies using transgenic ALS mice and primary motoneuron cultures. Its mechanism of action and target cells in the spinal cord, however, are largely unknown. Using mixed motoneuron cultures, motoneuron-like NSC34 cells, and primary astroglia cultures as model systems, we here demonstrate that angiogenin is a neuronally secreted factor that is endocytosed by astroglia and mediates neuroprotection in paracrine. We show that wild-type angiogenin acts unidirectionally to induce RNA cleavage in astroglia, while the ALS-associated K40I mutant is also secreted and endocytosed, but fails to induce RNA cleavage. Angiogenin uptake into astroglia requires heparan sulfate proteoglycans, and engages clathrin-mediated endocytosis. We show that this uptake mechanism exists for mouse and human angiogenin, and delivers a functional RNase output. Moreover, we identify syndecan 4 as the angiogenin receptor mediating the selective uptake of angiogenin into astroglia. Our data provide new insights into the paracrine activities of angiogenin in the nervous system, and further highlight the critical role of non-neuronal cells in the pathogenesis of ALS.

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Section: Discussionsupporting

confidence: 85%

Motoneurons Secrete Angiogenin to Induce RNA Cleavage in Astroglia

Skorupa

King²,

Aparicio³

et al. 2012

J. Neurosci.

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“…Plasma Membrane Microenvironment for Toxin Internalization-Sulfate group recognition contributes binding specificity for different heparin-binding proteins (41,42). The sulfate specificity of CTX A2 and A4 binding to heparin was investigated by competition SPR.…”

Section: Discussionmentioning

confidence: 99%

Endocytotic Routes of Cobra Cardiotoxins Depend on Spatial Distribution of Positively Charged and Hydrophobic Domains to Target Distinct Types of Sulfated Glycoconjugates on Cell Surface

Lee

Lin

Wang

et al. 2014

Journal of Biological Chemistry

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Background: Cobra venom consists of diverse toxin homologues important for prey capture through variable levels of gene duplication. Results: Comparative structural and cellular investigations revealed sensitivity of toxin homologues for extra-and intracellular targets via sulfated glycoconjugates. Conclusion: Variation in positively charged and hydrophobic domains in CTX homologues altered their target specificities and endocytosis. Significance: We provide a rationale for toxin homologues at cellular level to gain an evolutionary advantage.

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“…Given that the parameter space of possible reactivation procedures is essentially infinite, a generalized boundary condition may be difficult to prove at the behavioral level. This may explain part of the inconsistency in the field of boundary conditions of reconsolidation (Dreyfuss et al 2009). …”

Section: Reconsolidation Is Not Universalmentioning

confidence: 99%

Reconsolidation and the Dynamic Nature of Memory

Nader

2015

Cold Spring Harb Perspect Biol

136

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Memory reconsolidation is the process in which reactivated long-term memory (LTM) becomes transiently sensitive to amnesic agents that are effective at consolidation. The phenomenon was first described more than 50 years ago but did not fit the dominant paradigm that posited that consolidation takes place only once per LTM item. Research on reconsolidation was revitalized only more than a decade ago with the demonstration of reconsolidation in a well-defined behavioral protocol (auditory fear conditioning in the rat) subserved by an identified brain circuit (basolateral amygdala). Since then, reconsolidation has been shown in many studies over a range of species, tasks, and amnesic agents, and cellular and molecular correlates of reconsolidation have also been identified. In this review, I will first define the evidence on which reconsolidation is based, and proceed to discuss some of the conceptual issues facing the field in determining when reconsolidation does and does not occur. Last, I will refer to the potential clinical implications of reconsolidation.

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Heparan sulfate proteoglycans: structure, protein interactions and cell signaling

Cited by 209 publications

References 212 publications

Motoneurons Secrete Angiogenin to Induce RNA Cleavage in Astroglia

Motoneurons Secrete Angiogenin to Induce RNA Cleavage in Astroglia

Endocytotic Routes of Cobra Cardiotoxins Depend on Spatial Distribution of Positively Charged and Hydrophobic Domains to Target Distinct Types of Sulfated Glycoconjugates on Cell Surface

Reconsolidation and the Dynamic Nature of Memory

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