Experimentally, it has been proposed that C2B domains cooperate with the SNARE complexes in bringing the two membranes together. Analogously to what has been observed for the fusion stalk, the expansion of the fusion pore is also facilitated by a cooperation mechanism between Syt1-C2B domains. With selected mutations identified in previous experimental studies, such cooperative mechanism has been recently verified. These findings point to the relevance of PIP 2 strong anionic interactions with the polybasic patch in Syt1-C2B domains (KRLKKKKTTIKK, positions 321-332), in processes requiring high lipid remodeling, such as membrane bending, membrane fusion and the energetically costliest fusion pore expansion.