Dendritic spines show rapid motility and plastic morphology, which may mediate information storage in the brain. It is presently believed that polymerization/depolymerization of actin is the primary determinant of spine motility and morphogenesis. Here, we show that myosin IIB, a molecular motor that binds and contracts actin filaments, is essential for normal spine morphology and dynamics and represents a distinct biophysical pathway to control spine size and shape. Myosin IIB is enriched in the postsynaptic density (PSD) of neurons. Pharmacologic or genetic inhibition of myosin IIB alters protrusive motility of spines, destabilizes their classical mushroom-head morphology, and impairs excitatory synaptic transmission. Thus, the structure and function of spines is regulated by an actin-based motor in addition to the polymerization state of actin.
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"Several recent papers have addressed the role of myosin II in synaptic plasticity, including its role in spine morphology , AMPA receptor trafficking and memory (Ryu et al. 2006; Hodges et al. 2011; Rex et al. 2010; Gavin et al. 2012; Rubio et al. 2011). Myosin IIB is enriched in the postsynaptic density (PSD), is required for the maturation of spines and is essential for AMPA receptor-mediated EPSC amplitudes (Ryu et al. 2006). The phosphorylation status of the myosin II regulatory light chain can determine dendritic spine morphology (Hodges et al. 2011). "
"Morphological changes to a spine depend on actin dynamics12. In the hippocampus, myosin 2b is a key regulator of the changes in spine morphology related to learning and memory46. However, how and why neural spine morphology varies across the cortex remains unknown, especially in response to learning. "
[Show abstract][Hide abstract] ABSTRACT: Learning and memory depend on morphological and functional changes to neural spines. Non-muscle myosin 2b regulates actin dynamics downstream of long-term potentiation induction. However, the mechanism by which myosin 2b is regulated in the spine has not been fully elucidated. Here, we show that filamin A-interacting protein (FILIP) is involved in the control of neural spine morphology and is limitedly expressed in the brain. FILIP bound near the ATPase domain of non-muscle myosin heavy chain IIb, an essential component of myosin 2b, and modified the function of myosin 2b by interfering with its actin-binding activity. In addition, FILIP altered the subcellular distribution of myosin 2b in spines. Moreover, subunits of the NMDA receptor were differently distributed in FILIP-expressing neurons, and excitation propagation was altered in FILIP-knockout mice. These results indicate that FILIP is a novel, region-specific modulator of myosin 2b.
"Neurons were pretreated with 100 µM (S)-(−)-blebbistatin (aBL, the active form of blebbistatin), a myosin II ATPase blocker, for 30 min . In the presence of aBL, cLTP stimulation did not affect the localization of either drebrin or actin in dendritic spines (photomicrographs in Fig. 4), and failed to decrease the drebrin and actin SDRs (n = 30 cells; p = 0.37 for drebrin SDR at 5 min, p = 0.34 for actin SDR; Student's t test; graphs in Fig. 4). "
[Show abstract][Hide abstract] ABSTRACT: The neuronal actin-binding protein drebrin A forms a stable structure with F-actin in dendritic spines. NMDA receptor activation causes an exodus of F-actin bound by drebrin A (DA-actin) from dendritic spines, suggesting a pivotal role for DA-actin exodus in synaptic plasticity. We quantitatively assessed the extent of DA-actin localization to spines using the spine-dendrite ratio of drebrin A in cultured hippocampal neurons, and found that (1) chemical long-term potentiation (LTP) stimulation induces rapid DA-actin exodus and subsequent DA-actin re-entry in dendritic spines, (2) Ca(2+) influx through NMDA receptors regulates the exodus and the basal accumulation of DA-actin, and (3) the DA-actin exodus is blocked by myosin II ATPase inhibitor, but is not blocked by myosin light chain kinase (MLCK) or Rho-associated kinase (ROCK) inhibitors. These results indicate that myosin II mediates the interaction between NMDA receptor activation and DA-actin exodus in LTP induction. Furthermore, myosin II seems to be activated by a rapid actin-linked mechanism rather than slow MLC phosphorylation. Thus the myosin-II mediated DA-actin exodus might be an initial event in LTP induction, triggering actin polymerization and spine enlargement.