Processing of the matricellular protein hevin in mouse brain is dependent on ADAMTS4

Matt S. Weaver, Gail Workman, Marina Cardo-Vila, Wadih Arap, Renata Pasqualini, E. Helene Sage

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The matricellular SPARC family member hevin (SPARC-like 1/SPARCL-1/SC1/Mast9) contributes to neural development and alters tumor progression in a range of mammalian models. The distribution of hevin in mouse tissues was reexamined with a novel monoclonal antibody that discriminates between hevin and its ortholog SPARC. We now report proteolysis of hevin in many tissues, with the most extensive processing in the brain. We demonstrate a cleavage site within the hevin sequence for the neural tissue proteinase ADAMTS4. Digestion of hevin by ADAMTS4in vitro produced fragments similar to those present in brain lysates. Monoclonal antibodies revealed a SPARC-like fragment generated from hevin that was co-localized with ADAMTS4 in vivo. We show that proteolysis of hevin by ADAMTS4in the mouse cerebellum is important for the normal development of this tissue. In conclusion, we have identified the fragmentation of hevin by ADAMTS4 in the mouse brain and propose that this specific proteolysis is integral to cell morphology and extracellular matrix deposition in the developing brain.

Original languageEnglish (US)
Pages (from-to)5868-5877
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number8
DOIs
StatePublished - Feb 19 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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