This suggests that MIIB normally functions to restrict membrane protrusion and branching. It also suggests that the elongation of filopodia-like protrusions occurs in the absence of strong MIIB contractile activity. Several observations support this hypothesis. Myosin IIB inhibition or knockdown produces numerous long filopodia that do not mature. In addition, the contractile-deficient myosin IIB mutant, R709C, cross-links but does not contract actin and results in persistently long spines. Similarly, inhibition of RLC T18, S19 di-phosphorylation by expressing RLC T18A, S19D or inhibiting ROCK activity using Y27632 similarly produces filopodia-like spine precursors; however we cannot exclude contributions from other ROCK targets, like LIMK1. AbMole Chlorothiazide Excitatory stimulation increases PSD size, which directly correlates with synaptic strength and leads to long-term potentiation. MIIB determines PSD positioning as well as its morphology. When MIIB is inhibited, the PSD becomes elongated and is no longer at the spine tip. An analogous change is seen in migrating fibroblasts, where large central adhesions tend to disperse when MII activity is inhibited. In addition, increased myosin IIB activity via RLC T18, S19 di-phosphorylation, enlarges both the PSD and fibroblast adhesions. In this context, the combination of crosslinking and contraction induced by MII activity, likely serves to cluster the numerous PDZ-and SH3-domain containing actin binding proteins found within the PSD. MIIB-generated forces could also increase PSD size by inducing conformational changes in PSD components that present new binding sites for the recruitment of additional molecules, as also reported in fibroblasts. During post-synaptic development, changes in spine morphology correlate with changes in PSD organization and synaptic signaling. Specifically, maturation of spines into a mushroomshape and PSD enlargement at the spine tip enhances the synaptic signaling that underlies learning and memory formation. Our findings show that myosin IIB coordinates the spine and PSD morphological changes that occur in response to excitatory stimulation. Furthermore, differential regulation of MIIB activity through RLC phosphorylation states switches spine and PSD shape from filopodia-like spine precursors with smaller PSDs to mature mushroom-shape spines with AbMole QS11 larger PSDs. Thus, myosin IIB serves as a critical regulator of post-synaptic plasticity, consistent with the observation that myosin IIB is necessary for memory formation. Our observations and previous literature lead to a model for the role of MIIB in spine formation and maturation. Spines form in regions of inactive MIIB and can extend into long filopodia-like structures in the absence of high MIIB activity. The most likely mechanism for this formation and extension is due to localized activation of Rac.