Munc 18 and Munc 13 regulate early neurite outgrowth

• Published in: Biology of the cell 2010-08, Vol.102 (8), p.479-488
• Main Authors: Broeke, JHP, Roelandse, M, Luteijn, MJ, Boiko, T, Matus, A, Toonen, R F, Verhage, M
• Format: Article
• Language: English
• ISSN: 0248-4900
• DOI: 10.1042/BC20100036

Background information. During development, growth cones of outgrowing neurons express proteins involved in vesicular secretion, such as SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) proteins, Munc13 and Munc18. Vesicles are known to fuse in growth cones prior to synapse formation, which may contribute to outgrowth. Results. We tested this possibility in dissociated cell cultures and organotypic slice cultures of two release-deficient mice (Munc18-1 null and Mund 3-1/2 double null). Both types of release-deficient neurons have a decreased outgrowth speed and therefore have a smaller total neurite length during early development [DIV1-4 (day in vitro 1-4)]. In addition, more filopodia per growth cone were observed in Mund 8-1 null, but not WT (wild-type) or Mund 3-1/2 double null neurons. The smaller total neurite length during early development was no longer observed after synaptogenesis (DIV14-23). Conclusion. These data suggest that the inability of vesicle fusion in the growth cone affects outgrowth during the initial phases when outgrowth speed is high, but not during/after synaptogenesis. Overall, the outgrowth speed is probably not rate-limiting during neuronal network formation, at least in vitro. In addition, Mund 8, but not Mund 3, regulates growth cone filopodia, potentially via its previously observed effect on filamentous actin.