Chondroitin Sulfate Impairs Neural Stem Cell Migration Through ROCK Activation

Autor(es)

Galindo, Layla T. ^[1] ; Mundim, Mayara T. V. V. ^[1] ; Pinto, Agnes S. ^[1] ; Chiarantin, Gabrielly M. D. ^[1] ; Almeida, Maira E. S. ^[2] ; Lamers, Marcelo L. ^[3] ; Horwitz, Alan R. ^[4] ; Santos, Marinilce F. ^[5] ; Porcionatto, Marimelia ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Biochem, Neurobiol Lab, Rua Pedro de Toledo 669, 3 Andar, BR-04039032 Sao Paulo, SP - Brazil

^[2] Butantan Inst, Physiopathol Lab, BR-05503900 Sao Paulo - Brazil

^[3] Univ Fed Rio Grande do Sul, Dept Morphol Sci, BR-90050170 Porto Alegre, RS - Brazil

^[4] Univ Virginia, Dept Cell Biol, Sch Med, Charlottesville, VA 22903 - USA

^[5] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, BR-05508000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecular Neurobiology; v. 55, n. 4, p. 3185-3195, APR 2018.
• Citações Web of Science: 6

Resumo

Brain injuries such as trauma and stroke lead to glial scar formation by reactive astrocytes which produce and secret axonal outgrowth inhibitors. Chondroitin sulfate proteoglycans (CSPG) constitute a well-known class of extracellular matrix molecules produced at the glial scar and cause growth cone collapse. The CSPG glycosaminoglycan side chains composed of chondroitin sulfate (CS) are responsible for its inhibitory activity on neurite outgrowth and are dependent on RhoA activation. Here, we hypothesize that CSPG also impairs neural stem cell migration inhibiting their penetration into an injury site. We show that DCX+ neuroblasts do not penetrate a CSPG-rich injured area probably due to Nogo receptor activation and RhoA/ROCK signaling pathway as we demonstrate in vitro with neural stem cells cultured as neurospheres and pull-down for RhoA. Furthermore, CS-impaired cell migration in vitro induced the formation of large mature adhesions and altered cell protrusion dynamics. ROCK inhibition restored migration in vitro as well as decreased adhesion size. (AU)

• Processo FAPESP: 11/00526-7 - Estudo do papel dos membros da família das Rho GTPases no controle da migração de neuroblastos
• Beneficiário: Layla Testa Galindo
• Modalidade de apoio: Bolsas no Brasil - Doutorado