Integrin-Talin axis regulates mechanosensory presynaptic development and behavioral habituation to mechanical stimulation

From invertebrates to mammals, integrin signaling plays important roles in neuron development. β-Integrins are regulated by binding ECM, and through intracellular activation or inside-out signaling via Talin and Kindlin. While Integrins are known to regulate synapse formation and learning, much less is known about effects of Integrins, Talin and Kindlin on presynaptic branch formation and outcomes on behavior. Here, we use C. elegans as an in vivo model to study how the PAT-3/UNC-112/TLN-1 (β-integrin/Kindlin/Talin) signaling axis affects formation of presynaptic branches. Using a CRISPR-based, cell-specific degradation approach, we demonstrate that this Talin axis functions cell-autonomously in mechanosensory neurons to regulate presynaptic branch formation. Transgenic findings indicate TLN-1 inside-out signaling also influences branch formation. Thus, both impairing and activating Talin results in branch defects suggesting that balanced TLN-1 axis signaling is required for branch development. Genetic interaction and developmental time-course studies revealed that the TLN-1 axis functions in parallel with the RPM-1 (MYCBP2) ubiquitin ligase signaling hub to regulate both branch and presynaptic bouton formation. Consistent with the TLN-1 axis affecting presynaptic development in mechanosensory neurons, TLN-1 influences behavioral habituation to repeated low-threshold mechanical stimulation. Thus, our findings indicate that an Integrin-Talin axis functions cell-autonomously in mechanosensory neurons to regulate presynaptic development and behavioral habituation.