OVEREXPRESSION OF STMN2, A MICROTUBULE DESTABILIZING PROTEIN, ENHANCES PRESYNAPTIC NEUROTRANSMITTER RELEASE AND POSTSYNAPTIC RESPONSE

Stathmin-2 (STMN2) is a microtubule-binding protein associated to vesicles that promotes microtubule (MT) instability. It is well established that STMN2 is upregulated in neurons after injury, however, the synaptic relevance of a transient increase of STMN2 remains unknown. An upregulation of STMN2 was replicated on autaptic hippocampal neuronal cultures by lentiviral infection driving the expression of STMN2-GFP, and neurotransmission was recorded by whole cell patch-clamp technique. We discovered that STMN2 overexpression modified presynaptic properties by selectively enhancing spontaneous neurotransmitter release. We impaired the microtubule binding activity of STMN2 using anisomycin, which activates JNK-1 to phosphorylate STMN2 in specific residues. Anisomycin decreased spontaneous neurotransmitter release in STMN2 overexpressing neurons. In addition, we also tested anisomycin in neurons overexpressing phospho-null mutant STMN2. In this condition, neurons did not show a decrease in spontaneous neurotransmitter release. The effects of STMN2 on spontaneous neurotransmitter release were reverted upon MT acetylation. The effect was concentration dependent as revealed by the presence of 2.5 𝜇m-10 𝜇m ATAT1 in the internal recording solution. We also observed that STMN2 overexpression had a postsynaptic effect, as the amplitude of mEPSCs increased by 35%. Non-stationary noise analysis revealed that in neurons overexpressing STMN2 there was an increase in the insertion of glutamate receptors, while also promoting changes in the single channel conductance. Overexpression of STMN2 did not alter synapse density. Our findings could be key to explain the synaptic effects of the increase of STMN2 levels occurring upon neuronal injury.