Journal
MOLECULAR AND CELLULAR NEUROSCIENCE
Volume 41, Issue 4, Pages 397-408Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2009.04.004
Keywords
Fibronectin type III domains; Growth cone; Neurite outgrowth; Hippocampal neurons; Tenascin glycoprotein; Ig superfamily; beta 1 integrin; IP3; SERCA; Ryanodine receptor; Cell adhesion molecules; Protein kinase C; Calmodulin kinase
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Funding
- German Research Council (DFG) [642/A9]
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Tenascin-C (Tnc) is transiently expressed during neural development. Within its alternatively spliced fibronectin type III (TNfn) -motifs the TNfnD domain is Crucial for a neurite outgrowth-promoting region that is recognized by the GPI-linked adhesion molecule of the Ig-superfamily contactin. In order to understand the downstream signaling mechanisms, embryonic day E18 rat hippocampal neurons were cultivated on TNfnBD-containing and control substrates in the presence of various inhibitors. As predicted, axon outgrowth promotion Could be Suppressed by antibodies to the TNfnD domain, to contactin, or to the beta 1-integrin subunit. The chelators BAPTA/AM or EGTA as well as blockade of membrane-based Calcium channels or of the release of calcium from intracellular stores reduced axon growth to control levels. The inhibition of phospholipase C and its downstream targets protein kinase C or calmodulin kinase likewise blocked outgrowth promotion. We propose that TNfnBD stimulates the Outgrowth of hippocampal neurons by activating calcium- and phospholipase C-depending pathways. Digital video microscopy Studies revealed that increase of fiber length was caused by an augmentation of growth cone velocity. (c) 2009 Elsevier Inc. All rights reserved.
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