Hyalectanase Activities by the ADAMTS Metalloproteases

Fontanil, Tania; Mohamedi, Yamina; Casado, Jorge Espina; Obaya, Álvaro J.; Cobo, Teresa; Cal, Santiago

doi:10.3390/ijms22062988

Cited by 6 publications

(3 citation statements)

References 165 publications

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“…Fragments produced by proteolytic cleavage of CNS proteoglycans may not only be an indicator for the deconstruction of the intact ECM, but they could provide a gain of function by acting as matrikines. This term describes bioactive proteolytic (or glycosidic) fragments exerting signaling functions which may be different from the role of the uncleaved ECM components ( Ricard-Blum and Salza, 2014 ; Fontanil et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Brevican and Neurocan Cleavage Products in the Cerebrospinal Fluid - Differential Occurrence in ALS, Epilepsy and Small Vessel Disease

Hußler

Höhn

Stolz

et al. 2022

Front. Cell. Neurosci.

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The neural extracellular matrix (ECM) composition shapes the neuronal microenvironment and undergoes substantial changes upon development and aging, but also due to cerebral pathologies. In search for potential biomarkers, cerebrospinal fluid (CSF) and serum concentrations of brain ECM molecules have been determined recently to assess ECM changes during neurological conditions including Alzheimer’s disease or vascular dementia. Here, we measured the levels of two signature proteoglycans of brain ECM, neurocan and brevican, in the CSF and serum of 96 neurological patients currently understudied regarding ECM alterations: 16 cases with amyotrophic lateral sclerosis (ALS), 26 epilepsy cases, 23 cerebral small vessel disease (CSVD) patients and 31 controls. Analysis of total brevican and neurocan was performed via sandwich Enzyme-linked immunosorbent assays (ELISAs). Major brevican and neurocan cleavage products were measured in the CSF using semiquantitative immunoblotting. Total brevican and neurocan concentrations in serum and CSF did not differ between groups. The 60 kDa brevican fragment resulting from cleavage by the protease ADAMTS-4 was also found unchanged among groups. The presumably intracellularly generated 150 kDa C-terminal neurocan fragment, however, was significantly increased in ALS as compared to all other groups. This group also shows the highest correlation between cleaved and total neurocan in the CSF. Brevican and neurocan levels strongly correlated with each other across all groups, arguing for a joint but yet unknown transport mechanism from the brain parenchyma into CSF. Conclusively our findings suggest an ALS-specific pattern of brain ECM remodeling and may thus contribute to new diagnostic approaches for this disorder.

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Section: Discussionmentioning

confidence: 99%

Brevican and Neurocan Cleavage Products in the Cerebrospinal Fluid - Differential Occurrence in ALS, Epilepsy and Small Vessel Disease

Hußler

Höhn

Stolz

et al. 2022

Front. Cell. Neurosci.

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“…The hyalectanase family is composed of 7 members (ADAMTS-1, ADAMTS-4, ADAMTS-5, ADAMTS-8, ADAMTS-9, ADAMTS-15 and ADAMTS-20) which degrade proteoglycans such as aggrecan (ACAN), versican (VCAN), brevican and neurocan [ 50 ]. The last common ancestor of the hyalectanase genes was identified as the G96 gene for which the phenotype of interaction with ACAN and VCAN was gained ( Fig 10A ).…”

Section: Resultsmentioning

confidence: 99%

Phylogenetic inference of the emergence of sequence modules and protein-protein interactions in the ADAMTS-TSL family

Dennler,

Coste,

Blanquart

et al. 2023

PLoS Comput Biol

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Numerous computational methods based on sequences or structures have been developed for the characterization of protein function, but they are still unsatisfactory to deal with the multiple functions of multi-domain protein families. Here we propose an original approach based on 1) the detection of conserved sequence modules using partial local multiple alignment, 2) the phylogenetic inference of species/genes/modules/functions evolutionary histories, and 3) the identification of co-appearances of modules and functions. Applying our framework to the multidomain ADAMTS-TSL family including ADAMTS (A Disintegrin-like and Metalloproteinase with ThromboSpondin motif) and ADAMTS-like proteins over nine species including human, we identify 45 sequence module signatures that are associated with the occurrence of 278 Protein-Protein Interactions in ancestral genes. Some of these signatures are supported by published experimental data and the others provide new insights (e.g. ADAMTS-5). The module signatures of ADAMTS ancestors notably highlight the dual variability of the propeptide and ancillary regions suggesting the importance of these two regions in the specialization of ADAMTS during evolution. Our analyses further indicate convergent interactions of ADAMTS with COMP and CCN2 proteins. Overall, our study provides 186 sequence module signatures that discriminate distinct subgroups of ADAMTS and ADAMTSL and that may result from selective pressures on novel functions and phenotypes.

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“…This accumulation potentially excludes neurocan processing by other proteases. Neurocan cleavage not only by ADAMTS-12 but also by other ADAMTS family members could be crucial for normal maintenance of brain function (Tauchi et al, 2012;Gottschall and Howell, 2015;Fontanil et al, 2021). In this regard, neurocan has been related with important functions in brain development.…”

Section: Adamts-12 In Neurological Disordersmentioning

confidence: 99%

ADAMTS-12: Functions and Challenges for a Complex Metalloprotease

Mohamedi

Fontanil

Cal

et al. 2021

Front. Mol. Biosci.

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Nineteen members of the ADAMTS family of secreted zinc metalloproteinases are present in the human degradome. A wide range of different functions are being attributed to these enzymes and the number of their known substrates is considerably increasing in recent years. ADAMTSs can participate in processes such as fertility, inflammation, arthritis, neuronal and behavioral disorders, as well as cancer. Since its first annotation in 2001, ADAMTS-12 has been described to participate in different processes displayed by members of this family of proteinases. In this sense, ADAMTS-12 performs essential roles in modulation and recovery from inflammatory processes such as colitis, endotoxic sepsis and pancreatitis. ADAMTS-12 has also been involved in cancer development acting either as a tumor suppressor or as a pro-tumoral agent. Furthermore, participation of ADAMTS-12 in arthritis or in neuronal disorders has also been suggested through degradation of components of the extracellular matrix. In addition, ADAMTS-12 proteinase activity can also be modified by interaction with other proteins and thus, can be an alternative way of modulating ADAMTS-12 functions. In this review we revised the most relevant findings about ADAMTS-12 function on the 20th anniversary of its identification.

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Hyalectanase Activities by the ADAMTS Metalloproteases

Cited by 6 publications

References 165 publications

Brevican and Neurocan Cleavage Products in the Cerebrospinal Fluid - Differential Occurrence in ALS, Epilepsy and Small Vessel Disease

Brevican and Neurocan Cleavage Products in the Cerebrospinal Fluid - Differential Occurrence in ALS, Epilepsy and Small Vessel Disease

Phylogenetic inference of the emergence of sequence modules and protein-protein interactions in the ADAMTS-TSL family

ADAMTS-12: Functions and Challenges for a Complex Metalloprotease

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