The ADAMTS hyalectanase family: biological insights from diverse species

Dancevic, Carolyn M.; McCulloch, Daniel R.; Ward, Alister C.

doi:10.1042/bcj20160148

Cited by 15 publications

(19 citation statements)

References 148 publications

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“…We focussed on expression of specific ECM components identified as up-regulated, and used quantitative PCR to confirm the changes in expression detected by RNA-seq. PCR analysis of RNA isolated from new MEF preparations confirmed that message levels for fibrillin 2 (which forms elastic microfibrils within the ECM [ 38 ]), adamts15 (a matrix-associated peptidase [ 39 ]), and FRAS1 (Fraser extracellular matrix complex 1 –an ECM component abundant in basement membrane [ 40 ]), are all highly up-regulated in CAV1-/- MEFS ( Fig 2A ).…”

Section: Resultsmentioning

confidence: 99%

Cells respond to deletion of CAV1 by increasing synthesis of extracellular matrix

et al. 2018

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A range of cellular functions have been attributed to caveolae, flask-like invaginations of the plasma membrane. Here, we have used RNA-seq to achieve quantitative transcriptional profiling of primary embryonic fibroblasts from caveolin 1 knockout mice (CAV1-/- MEFs), and thereby to gain hypothesis-free insight into how these cells respond to the absence of caveolae. Components of the extracellular matrix were decisively over-represented within the set of genes displaying altered expression in CAV1-/- MEFs when compared to congenic wild-type controls. This was confirmed biochemically and by imaging for selected examples. Up-regulation of components of the extracellular matrix was also observed in a second cell line, NIH-3T3 cells genome edited to delete CAV1. Up-regulation of components of the extracellular matrix was detected in vivo by assessing collagen deposition and compliance of CAV1-/- lungs. We discuss the implications of these findings in terms of the cellular function of caveolae.

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Section: Resultsmentioning

confidence: 99%

Cells respond to deletion of CAV1 by increasing synthesis of extracellular matrix

et al. 2018

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“…The phenotypes induced by the adamts5 morphants were rescued with mRNA encoding both wild-type and catalytically-inactive ADAMTS5. Although unexpected, there is some precedence for ADAMTS family members demonstrating non-catalytic functions as reviewed recently [ 35 ]. For example, ADAMTS1 has been shown to bind to VEGF through its C-terminal thrombospondin repeats and spacer domain to block VEGFR2 activation [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

The ADAMTS5 Metzincin Regulates Zebrafish Somite Differentiation

Dancevic

Gibert

Berger

et al. 2018

IJMS

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The ADAMTS5 metzincin, a secreted zinc-dependent metalloproteinase, modulates the extracellular matrix (ECM) during limb morphogenesis and other developmental processes. Here, the role of ADAMTS5 was investigated by knockdown of zebrafish adamts5 during embryogenesis. This revealed impaired Sonic Hedgehog (Shh) signaling during somite patterning and early myogenesis. Notably, synergistic regulation of myod expression by ADAMTS5 and Shh during somite differentiation was observed. These roles were not dependent upon the catalytic activity of ADAMTS5. These data identify a non-enzymatic function for ADAMTS5 in regulating an important cell signaling pathway that impacts on muscle development, with implications for musculoskeletal diseases in which ADAMTS5 and Shh have been associated.

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“…The ADAMTSs are a family of secreted proteins that is composed of 19 members in mammals [60,61]. ADAMTSs are involved in a wide variety of physiological and pathological processes that include, among other things, their participation in the degradation and thus the remodeling of components of the extracellular matrix, the inhibition of angiogenesis, and the regulation of inflammatory processes [61,62].…”

Section: Adamtss In the Cnsmentioning

confidence: 99%

New Insights into ADAMTS Metalloproteases in the Central Nervous System

et al. 2020

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Components of the extracellular matrix (ECM) are key players in regulating cellular functions throughout the whole organism. In fact, ECM components not only participate in tissue organization but also contribute to processes such as cellular maintenance, proliferation, and migration, as well as to support for various signaling pathways. In the central nervous system (CNS), proteoglycans of the lectican family, such as versican, aggrecan, brevican, and neurocan, are important constituents of the ECM. In recent years, members of this family have been found to be involved in the maintenance of CNS homeostasis and to participate directly in processes such as the organization of perineural nets, the regulation of brain plasticity, CNS development, brain injury repair, axonal guidance, and even the altering of synaptic responses. ADAMTSs are a family of “A disintegrin and metalloproteinase with thrombospondin motifs” proteins that have been found to be involved in a multitude of processes through the degradation of lecticans and other proteoglycans. Recently, alterations in ADAMTS expression and activity have been found to be involved in neuronal disorders such as stroke, neurodegeneration, schizophrenia, and even Alzheimer’s disease, which in turn may suggest their potential use as therapeutic targets. Herein, we summarize the different roles of ADAMTSs in regulating CNS events through interactions and the degradation of ECM components (more specifically, the lectican family of proteoglycans).

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The ADAMTS hyalectanase family: biological insights from diverse species

Cited by 15 publications

References 148 publications

Cells respond to deletion of CAV1 by increasing synthesis of extracellular matrix

Cells respond to deletion of CAV1 by increasing synthesis of extracellular matrix

The ADAMTS5 Metzincin Regulates Zebrafish Somite Differentiation

New Insights into ADAMTS Metalloproteases in the Central Nervous System

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