β1-integrin alters ependymal stem cell BMP receptor localization and attenuates astrogliosis after spinal cord injury

Hilary A. North*, Liuliu Pan, Tammy L. McGuire, Sarah Brooker, John A. Kessler

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Astrogliosis after spinal cord injury (SCI) is a major impediment to functional recovery. More than half of new astrocytes generated after SCI are derived from ependymal zone stem cells (EZCs). We demonstrate that expression of |31-integrin increases in EZCs following SCI in mice. Conditional knock-out of /31-integrin increases GFAP expression and astrocytic differentiation by cultured EZCs without altering oligodendroglial or neuronal differentiation. Ablation of |31-integrin from EZCs in vivo reduced the number of EZC progeny that continued to express stem cell markers after SCI, increased the proportion of EZCprogeny that differentiated into GFAP + astrocytes, and diminished functional recovery. Loss of /31-integrin increased SMAD1/5/8 and p38 signaling, suggesting activation of BMP signaling. Coimmunoprecipitation studies demonstrated that /31-integrin directly interacts with the bone morphogenetic protein receptor sub-units BMPR1a and BMPR1b. Ablation of/31-integrin reduced overall levels of BMP receptors but significantly increased partitioning of BMPR1b into lipid rafts with increased SMAD1/5/8 and p38 signaling. Thus /31-integrin expression by EZCs reduces movement of BMPR1b into lipid rafts, thereby limiting the known deleterious effects of BMPR1b signaling on glial scar formation after SCI.

Original languageEnglish (US)
Pages (from-to)3725-3733
Number of pages9
JournalJournal of Neuroscience
Volume35
Issue number9
DOIs
StatePublished - 2015

Keywords

  • Astrocyte
  • BMP
  • Integrin
  • Neural stem cell
  • Spinal cord injury

ASJC Scopus subject areas

  • Neuroscience(all)

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