Protocadherins are the largest subfamily of the cadherin superfamily and are also heavily implicated in neurodevelopmental disorders such as ID and ASD. The signaling mechanisms linking the diverse protocadherins to the actin cytoskeleton in neurons are still being worked out.Recent studies, however, show that the protocadherins PCDH and PCDH directly recruit the WAVE complex in the intracellular tail. Remarkably, the WIRS motif appears to be present in at least proteins, many of which are adhesion molecules, including protocadherins.LTP is a process in which periods of high frequency Granisetron hydrochloride synaptic activity lead to a longlasting increase in the strength of a synapse.LTD occurs after periods of low frequency synaptic activity lead to a decrease in synaptic strength.Although LTP and LTD involve many longlasting changes at the receptor, signaling, and gene expression levels, we will focus here on two of these alterations that are modulated by actin remodeling and that occur in CA hippocampal dendritic spines.The first evidence to suggest that the actin cytoskeleton was important for AMPAR localization came from studies in cultured hippocampal neurons that were exposed to actindepolymerizing drugs such as latrunculin A, which sequesters monomeric actin.Loss of filamentous actin led to reduced AMPAR receptors in dendritic spines. This suggests that cofilin has a receptorspecific effect on AMPAR diffusion.WASH is a recently discovered endocytic compartment NPF that binds to lipids and is ubiquitously expressed.There are five proteins in the WASH complex: SWIP. As proteins are sorted, the WASH complex is thought to provide endosomal membrane domains through the polymerization of actin into which different proteins can be organized. VPS, a component of the retromer complex, localizes to dendritic spines, and expression of a VPS lossoffunction mutation leads to altered AMPAR surface expression and synaptic recycling and is also linked to familial parkinsonism. However, further work is needed to functionally test the consequences of this mutation in SWIP.Together, these data suggest that OPHN operates in a multifaceted manner to coordinate actin cytoskeletal remodeling and endocytosis mechanisms in spines.The ability of OPHN to influence glutamate receptor trafficking may be one important clue into the mechanisms underlying how the loss of OPHN leads to ID in humans. Studies in the mids showed that synaptic activation increases spine volume and that these morphological changes persisted longterm, synaptic strength. Spine Pancuronium bromide structural plasticity is an actindependent process and is linked to functional changes associated with LTP and LTD in spines activation through calcium influx. Interestingly, this rate of turnover is also subdomainspecific: low at perisynaptic endocytic zones and faster at filaments near the PSD. Regardless of zone, actin filaments treadmill constitutively, with filament lifetimes lasting less than min. Increased actin density in dendritic spines is seen in vivo for up to weeks following electrical LTP induction. Loss of WAVE, however, enhances LTP, impairs LTD, and alters the morphology of synapses and a wide range of behaviors, including learning and memory. There are three highly conserved cofilin genes with differing expression patterns: mcofilin, and ADF.Further, genetic loss of ncofilin leads to an increase and enlargement of spines in vivo as well as impairment of rewardinduced and fearconditioned learning.