Plasmin-mediated Release of the Guidance Molecule F-spondin from the Extracellular Matrix

Vered Tzarfaty-Majar, Roser López-Alemany, Yael Feinstein, Lourdes Gombau, Orit Goldshmidt, Eduardo Soriano, Pura Muñoz-Cánoves*, Avihu Klar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Serine proteases are implicated in a variety of processes during neurogenesis, including cell migration, axon outgrowth, and synapse elimination. Tissue-type plasminogen activator and urokinase-type activator are expressed in the floor plate during embryonic development. F-spondin, a gene also expressed in the floor plate, encodes a secreted, extracellular matrix-attached protein that promotes outgrowth of commissural axons and inhibits outgrowth of motor axons. F-spondin is processed in vivo to yield an amino half protein that contains regions of homology to reelin and mindin, and a carboxyl half protein that contains either six or four thrombospondin type I repeats (TSRs). We have tested F-spondin to see whether it is subjected to processing by plasmin and to determine whether the processing modulates its biological activity. Plasmin cleaves F-spondin at its carboxyl terminus. By using nested deletion proteins and mutating potential plasmin cleavage sites, we have identified two cleavage sites, the first between the fifth and sixth TSRs, and the second at the fifth TSR. Analysis of the extracellular matrix (ECM) attachment properties of the TSRs revealed that the fifth and sixth TSRs bind to the ECM, but repeats 1-4 do not. Structural functional experiments revealed that two basic motives are required to elicit binding of TSR module to the ECM. We demonstrate further that plasmin releases the ECM-bound F-spondin protein.

Original languageAmerican English
Pages (from-to)28233-28241
Number of pages9
JournalJournal of Biological Chemistry
Issue number30
StatePublished - 27 Jul 2001


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