The Membrane And Its Effects On Human Development

860 Words Oct 21st, 2015 4 Pages
It is generally accepted that resting CaMKIIβ bundles and stabilizes actin cytoskeleton. Transient activation of CaMKIIβ relaxes cytoskeleton, promotes actin polymerization and CaMKIIβ recruitment, and favors cytoskeleton growth. This model has been shown in both synaptogenesis (Okamoto et al., 2007) and OL maturation (Waggener et al., 2013). Based on this theory, we proposed that prolonged CaMKIIβ activation by NMDA-R-mediated Ca2+ influx leads to destabilization of actin cytoskeleton and membrane disintegration in mature OLs. Although our experiments unambiguously showed that NMDA-R activation results in CaMKIIβ activation, direct proof that links CaMKIIβ activation and membrane reduction are lacking. All the existing CaMKIIβ inhibitors are either non-specific or highly toxic to OLs (usually kills cells within 6 h). Since the membrane reduction in OLs is a long-term phenomenon (usually happened after 12 h, and persists at least 48 h), pharmacologically blocking CaMKIIβ activation is unrealistic. Although an ON-TARGETplus SMARTpool siRNA specifically against mice Camk2b were commercially available, we failed to find an effective way to deliver the siRNA into mature, adherent OLs. Plus, hypomyelination in ventral spinal cord has been reported in CaMKIIβ KO mice, suggesting that silencing CaMK2b gene itself already had an impact on actin cytoskeleton. Thus inhibiting CaMKIIβ expression may also not be an ideal way to assess whether mature OL membrane reduction is the result…
Open Document