METHYL-CpG-BINDING PROTEIN 2 IS LOCALIZED IN THE POSTSYNAPTIC COMPARTMENT: AN IMMUNOCHEMICAL STUDY OF SUBCELLULAR FRACTIONS

Rett syndrome (RS) is a developmental neurologic disordercharacterized by severe cognitive impairment, autisticbehavior, stereotypic movements, and frequently also seizures(Naidu, 1997). The disorder is associated in a majorityof cases with mutations of the coding region of thegene for methyl-CpG-binding protein 2 (MeCP2) (Shahbazianand Zoghbi, 2001; Hoffbuhr et al., 2001). More recently,other neurologic syndromes different from RS havebeen reported as associated with MeCP2 mutations (Imessaoudeneet al., 2001; Watson et al., 2001; Dotti et al.,2002). Only limited data are available about the expressionof MeCP2 in the CNS. These immunochemical studiesdescribe a predominant neuronal compartmentalization(LaSalle et al., 2001; Shahbazian et al., 2002), and apattern of expression that parallels neuronal differentiation(Akbarian et al., 2001; Shahbazian et al., 2002). Despitethis information, and considering that MeCP2 has widetissue distribution (LaSalle et al., 2001; Shahbazian et al.,2002), it is still unclear why abnormal MeCP2 expression ismainly associated with neurologic dysfunction. Moreover,recent data show that several transcription factors, withexpression in the CNS and other organs, may have aunique neuronal distribution characterized by both nuclearand synaptic localizations (Paratcha et al., 2000; Eberwineet al., 2001). For these reasons, we examined MeCP2expression in normal human neocortex with special emphasison its subcellular localization.