Laminin modulates neuritogenesis of developing rat retinal ganglion cells through a protein kinase C-dependent pathway.
Dissociated cells from rat retinae (P2-P21) were cultured to investigate interactions between brain-derived neurotrophic factor (BDNF), various substrates (poly-L-lysine, collagen, and laminin), and protein kinases upon the neuritogenesis of retinal ganglion cells (RGCs). We found that BDNF-promoted neuritogenesis was enhanced by forskolin in RGCs from rats at P2-P21 plated on either poly-L-lysine or collagen. In contrast, in cultures with a laminin substrate, the enhancer effect of forskolin was observed only in RGCs taken from the retina of rats at P2-P6. Laminin blocked the enhancement of BDNF-induced RGCs neuritogenesis by forskolin, in RGCs from either P14 or P21, and induced a tenfold increase of protein kinase C (PKC) activity compared to poly-L-lysine. This blockade was reverted with a selective PKC inhibitor and was reproduced in poly-L-lysine cultures of P14-P21 RGCs with a PKC activator. Because axotomized RGCs need both BDNF and forskolin to regenerate, we suggest that laminin can hinder this effect by simultaneous PKC activation according to a developmentally regulated pattern. We further propose a model of interaction in the optic pathways triggered by BDNF, forskolin, and laminin that may be useful in elucidating some of the biological effects seen with regenerating axons.
de Ary-Pires
R
R
Instituto de Biofísica da UFRJ, Rio de Janeiro, Brazil.
Linden
R
R
D000818:Animals; D001711:Biotransformation / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism; D007797:Laminin / Q000378:metabolism / Q000502:physiology*; D016501:Neurites / Q000502:physiology*; D011107:Polylysine / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D012165:Retinal Ganglion Cells / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D007797:Laminin; D005576:Colforsin; D011107:Polylysine; D003094:Collagen; D011493:Protein Kinase C