Coordinate regulation of cadherin and integrin function by the chondroitin sulfate proteoglycan neurocan

Hedong Li, Tin Chung Leung, Stanley Hoffman, Janne Balsamo, Jack Lilien

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

N-cadherin and β1-integrins play decisive roles in morphogenesis and neurite extension and are often present on the same cell. Therefore, the function of these two types of adhesion systems must be coordinated in time and space to achieve the appropriate cell and tissue organization. We now show that interaction of the chondroitin sulfate proteoglycan neurocan with its GalNAcPTase receptor coordinately inhibits both N-cadherin- and β1- integrin-mediated adhesion and neurite outgrowth. Furthermore, the inhibitory activity is localized to an NH2-terminal fragment of neurocan containing an Ig loop and an HA-binding domain. The effect of neurocan on β1-integrin function is dependent on a signal originating from the cadherin cytoplasmic domain, possibly mediated by the nonreceptor protein tyrosine kinase Fer, indicating that cadherin and integrin engage in direct cross-talk. In the developing chick, neural retina neurocan is present in the inner plexiform layer from day 7 on, and the GalNAcPTase receptor becomes restricted to the inner nuclear layer and the ganglion cell layer (as well as the fiber layer), the two forming a sandwich. These data suggest that the coordinate inhibition of cadherin and integrin function on interaction of neurocan with its receptor may prevent cell and neurite migration across boundaries.

Original languageEnglish (US)
Pages (from-to)1275-1288
Number of pages14
JournalJournal of Cell Biology
Volume149
Issue number6
DOIs
StatePublished - Jun 12 2000
Externally publishedYes

Keywords

  • Adhesion
  • Cadherin
  • Integrin
  • Neurite outgrowth
  • Tyrosine kinase Fer

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'Coordinate regulation of cadherin and integrin function by the chondroitin sulfate proteoglycan neurocan'. Together they form a unique fingerprint.

Cite this