UPREGULATION OF STATHMIN-2 INDUCES MICROTUBULE DEPENDENT SYNAPTIC MODIFICATIONS

Stathmin-2 (STMN2) is a microtubule-associated protein that promotes microtubule instability and is targeted to vesicles. It is well established that STMN2 is upregulated after injury, however, the biological relevance and the mechanisms activated by a transient increase of STMN2 remain unknown. The expression of STMN2-APEX2-mSCarlet in cultured hippocampal neurons revealed that STMN2 is transported in ~100 nm diameter vesicles found in axonal and dendritic locations. STMN2 vesicles move throughout the axon and dendritic tree by alternating directed movements and pauses. Co-expression of GFP-STMN2 and EB3-tdtomato showed that microtubule dynamics are locally (<8 mm) enhanced by vesicles transporting STMN2. Microtubule growth was not altered upon phosphorylation of STMN2 driven by JNK-1 activation. Glutamate release was investigated by expressing the glutamate sensor SF-iGluSnFR.S72A in the astrocytic feeder layer of hippocampal cultures. This approach allows to detect synaptic activity without interfering with neuronal properties. The position of vesicles transporting mScarlet-STMN2 was associated with the location of synapses. Overexpression of pScarlet-hSTMN2 enhanced spontaneous but did not affect evoked neurotransmitter release. Altogether, these results show that STMN2 exerts a localized effect on microtubule dynamics. Considering the fundamental role of spontaneous neurotransmitter release in the assembly of neuronal circuits, we suggest a link between STMN2, microtubule dynamics and spontaneous neurotransmitter release to promote the formation of new synaptic contacts.