Perlecan is recruited by dystroglycan to nodes of Ranvier and binds the clustering molecule gliomedin

Colombelli, Cristina; Palmisano, Marilena; Eshed-Eisenbach, Yael; Zambroni, Desirée; Pavoni, Ernesto; Ferri, Cinzia; Saccucci, Stefania; Nicole, Sophie; Soininen, Raija; McKee, Karen K.; Yurchenco, Peter D.; Peles, Elior; Wrabetz, Lawrence; Feltri, M. Laura

doi:10.1083/jcb.201403111

Cited by 37 publications

(41 citation statements)

References 90 publications

(184 reference statements)

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“…Disrupting perlecan:α/β-dystroglycan interactions compromises basement membrane stability 150 . Recently, it was discovered that perlecan is recruited to the nodes of Ranvier and participates in rapid neural conduction 151 . Dystroglycan selectively recruits perlecan as a novel component of the nodal matrix and is involved in nodogenesis via gliomedin clustering 151 (Figure 3).…”

Section: Perlecan Receptors: a Dual Receptor Antagonismmentioning

confidence: 99%

Decoding the Matrix: Instructive Roles of Proteoglycan Receptors

2015

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The extracellular matrix is a dynamic repository harboring instructive cues that embody substantial regulatory dominance over many evolutionarily conserved intracellular activities including proliferation, apoptosis, migration, motility, and autophagy. The matrix also coordinates and parses hierarchical information, such as angiogenesis, tumorigenesis, and immunological responses, typically providing the critical determinants driving each outcome. We provide the first comprehensive review focused on proteoglycan receptors, that is, signaling transmembrane proteins that use secreted proteoglycans as ligands, in addition to their natural ligands. The majority of these receptors belong to an exclusive subset of receptor tyrosine kinases and assorted cell surface receptors that specifically bind, transduce, and modulate fundamental cellular processes following interactions with proteoglycans. The class of small leucine-rich proteoglycans is the most studied so far, and constitutes the best understood example of proteoglycan/receptor interactions. Decorin and biglycan evoke autophagy and immunological responses that deter, suppress, or exacerbate pathological conditions such as tumorigenesis, angiogenesis, and chronic inflammatory disease. Basement membrane-associated heparan sulfate proteoglycans - perlecan, agrin and collagen XVIII - represent a unique cohort and provide proteolytically-cleaved bioactive fragments for modulating cellular behavior. The receptors that bind the genuinely multifactorial and multivalent proteoglycans represent a nexus in understanding basic biological pathways and opens new avenues for therapeutic and pharmacological intervention.

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Section: Perlecan Receptors: a Dual Receptor Antagonismmentioning

confidence: 99%

Decoding the Matrix: Instructive Roles of Proteoglycan Receptors

2015

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“…An example of proteoglycan versatility comes in the form of perlecan, an immense heparan sulfate proteoglycan primarily localized to basement membranes and pericellular spaces [4–9]. The modular structure of perlecan enables homeostatic regulation within a vast array of cellular processes including cell adhesion [10,11], endocytosis [12], bone and cartilage formation [13–16], lipid metabolism [17], peripheral node assembly [18], inflammation and wound healing [19,20], thrombosis [21], cancer angiogenesis [9,11,22–33], cardiovascular development [34], and autophagy [35,36]. Given the gargantuan structure and multitude of functions of perlecan, it is no surprise that its gene, HSPG2 , is similarly large and transcriptionally controlled by complex promoter interactions.…”

Section: Introductionmentioning

confidence: 99%

A current view of perlecan in physiology and pathology: A mosaic of functions

2017

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Perlecan, a large basement membrane heparan sulfate proteoglycan, is expressed in a wide array of tissues where it regulates diverse cellular processes including bone formation, inflammation, cardiac development, and angiogenesis. Here we provide a contemporary review germane to the biology of perlecan encompassing its genetic regulation as well as an analysis of its modular protein structure as it pertains to function. As perlecan signaling from the extracellular matrix converges on master regulators of autophagy, including AMPK and mTOR, via a specific interaction with vascular endothelial growth factor receptor 2, we specifically focus on the mechanism of action of perlecan in autophagy and angiogenesis and contrast the role of endorepellin, the C-terminal fragment of perlecan, in these cellular and morphogenic events.

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“…In addition, perlecan promoter can be positively regulated by TGF-β [131, 132] and negatively regulated by interferon-γ [133], making perlecan an early response gene. A novel interaction of this proteoglycan has been found at nodes of Ranvier, where perlecan directly interacts with the neurofascin-glial ligand, gliomedin [134]. …”

Section: Perlecan a Large Multimodular Heparan Sulfate Proteoglycanmentioning

confidence: 99%

“…Perlecan can regulate murine neurogenesis during telencephalon development [161] and can intensify clustering of components of nodes of Ranvier, by double binding to both dystroglycan and gliomedin [134]. Thus, perlecan might be involved in normal or pathological processes relating to peripheral nodes, since Na + -channel accumulation and fast conduction are mediated by nodes of Ranvier.…”

Section: Perlecan a Large Multimodular Heparan Sulfate Proteoglycanmentioning

confidence: 99%

Endostatin and endorepellin: A common route of action for similar angiostatic cancer avengers

Poluzzi

Iozzo

Schaefer

2016

Advanced Drug Delivery Reviews

111

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Traditional cancer therapy typically targets the tumor proper. However, newly-formed vasculature exerts a major role in cancer development and progression. Autophagy, as a biological mechanism for clearing damaged proteins and oxidative stress products released in the tumor milieu, could help in tumor resolution by rescuing cells undergoing modifications or inducing autophagic-cell death of tumor blood vessels. Cleaved fragments of extracellular matrix proteoglycans are emerging as key players in the modulation of angiogenesis and endothelial cell autophagy. An essential characteristic of cancer progression is the remodeling of the basement membrane and the release of processed forms of its constituents. Endostatin, generated from collagen XVIII, and endorepellin, the C-terminal segment of the large proteoglycan perlecan, possess a dual activity as modifiers of both angiogenesis and endothelial cell autophagy. Manipulation of these endogenously-processed forms, located in the basement membrane within tumors, could represent new therapeutic approaches for cancer eradication.

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Perlecan is recruited by dystroglycan to nodes of Ranvier and binds the clustering molecule gliomedin

Abstract: Dystroglycan promotes nodogenesis in part through recruitment of perlecan to nodes of Ranvier, where it binds to gliomedin and may thereby promote sodium channel clustering.

Cited by 37 publications

References 90 publications

Decoding the Matrix: Instructive Roles of Proteoglycan Receptors

Decoding the Matrix: Instructive Roles of Proteoglycan Receptors

A current view of perlecan in physiology and pathology: A mosaic of functions

Endostatin and endorepellin: A common route of action for similar angiostatic cancer avengers

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