Asymmetric Turning Mechanisms

Science's STKE  02 Jan 2007:
Vol. 2007, Issue 367, pp. tw4
DOI: 10.1126/stke.3672007tw4

Asymmetric Ca2+ signals inside neuronal growth cones can mediate attractive or repulsive turning. Localized increases in growth cone Ca2+ concentration that elicit Ca2+-induced Ca2+ release (CICR) are attractive (the growth cone turns toward the side with greater Ca2+ concentration), whereas signals that do not elicit CICR are repulsive (the growth cone turns away from the side with greater Ca2+ concentration). Using localized photolysis of caged Ca2+ to elicit asymmetric increases in Ca2+ in the growth cones of cultured chick dorsal root ganglion neurons, Tojima et al. manipulated CICR pharmacologically or through culture on different substratum to generate attractive or repulsive turning. Attractive Ca2+ signals led to the microtubule-dependent migration of fluorescently labeled vesicles from the central to the peripheral region of the growth cone on the side with the Ca2+ increase, whereas repulsive Ca2+ signals had no effect on vesicle trafficking. The vesicles contained VAMP2 (vesicle-associated membrane protein 2, a SNARE protein implicated in Ca2+-dependentvesicle fusion with the membrane). When vesicles were labeled with a pH-sensitive fluorescent VAMP2 fusion protein, experiments indicated that attractive Ca2+ signalsstimulated asymmetric VAMP2-mediated exocytosis. Pharmacological blockade of VAMP2-mediated exocytosis blocked turning to attractive Ca2+ signals or toward attractive cues (nerve growth factor or myelin-associated glycoprotein), but not axon growth or repulsive turning. Thus, the authors conclude that attractive—but not repulsive—growth cone turning depends on asymmetric vesicle trafficking and exocytosis.

T. Tojima, H. Akiyama, R. Itofusa, Y. Li, H. Katayama, A. Miyawaki, H. Kamiguchi, Attractive axon guidance involves asymmetric membrane transport and exocytosis in the growth cone. Nat. Neurosci. 10, 58-66 (2007). [PubMed]