Evidence for the involvement of lfc on the MAG induced growth cone collapse

JOSÉ WOJNACKI; GONZALO QUASSOLLO; LAURA GASTALDI; CECILIA CONDE; ALFREDO CÁCERES

Santa Cruz

Workshop; Workshop: Emerging Concepts on Neuronal Cytoskeleton; 2011

Studies on sensory axon regeneration have well established that inhibitory molecules -MAG, OMgp and NogoA– present in the lesionedenvironment surrounding the tip of the regenerating axon, act through a common tripartite receptor composed of p75 NTR, Nogo receptor and lingo-1 (Domeniconi et al, 2002; Domeniconi et al, 2005; Liu et al, 2002; Schnaar at al, 2009) . This complex relays the inhibitory signal to the small GTPase Rho-A releasing it from the GDI inhibitory cap, thus activating Rho-A and its down stream effectors leading to growth cone collapse and axonal retraction (Lehmann et al, 1999; Alabed et al, 2009; Dergham et al, 2002;) . This mechanism could lead to rapid and local RhoA activation but it's not clear whether this mechanism could maintain the sustained activation of Rho-A seen during growth cone collapse. Recently our laboratory has established that the RhoA GEF, Lfc, is involved in the inhibitory signal that  ensures that only one of the several neurites seen during early  hippocampal neuron development differentiates into an axon (Conde et al, 2010). Given this key role during hippocampal neuronal development, it's possible that this particular GEF, Lfc, may have a central role relaying the inhibitory signal from myelin components to one of the central acting dynamics regulator, the small GTPase Rho-A.In this work we present the first evidence suggesting that Lfc is  important to maintain the sustained activity of RhoA during MAG induced growth cone collapse. In particular we have established that: 1) DRG sensory neurons express this RhoA GEF and that it's distributed along the axon and concentrated within the growth cone; and 2) that Lfc relocates and concentrates to a microtubules free area within the the neuronal growth cone after MAG treatment.