Filamin A and Filamin B are co-expressed within neurons during periods of neuronal migration and can physically interact

Volney L. Sheen, Yuanyi Feng, Donna Graham, Toshiro Takafuta, Sandor S. Shapiro, Christopher A. Walsh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

118 Scopus citations


Mutations in the X-linked gene Filamin A (FLNA) lead to the human neurological disorder, periventricular heterotopia (PH). Although PH is characterized by a failure in neuronal migration into the cerebral cortex with consequent formation of nodules in the ventricular and subventricular zones, many neurons appear to migrate normally, even in males, suggesting compensatory mechanisms. Here we characterize expression patterns for FlnA and a highly homologous protein Filamin B (FlnB) within the nervous system, in order to better understand their potential roles in cortical development. FlnA mRNA was widely expressed in all cortical layers while FlnB mRNA was most highly expressed in the ventricular and subventricular zones during development. In adulthood, widespread but reduced expression of FlnA and FlnB persisted throughout the cerebral cortex. FlnA and FlnB proteins were highly expressed in both the leading processes and somata of migratory neurons during corticogenesis. Postnatally, FlnA immunoreactivity was largely localized to the cell body with FlnB in the soma and neuropil during neuronal differentiation. In adulthood, diminished expression of both proteins localized to the cell soma and nucleus. Moreover, the putative FLNB homodimerization domain strongly interacted with itself or the corresponding homologous region of FLNA by yeast two-hybrid interaction, the two proteins co-localized within neuronal precursors by immunocytochemistry and the existence of FLNA-FLNB heterodimers could be detected by co-immunoprecipitation. These results suggest that FLNA and FLNB may form both homodimers and heterodimers and that their interaction could potentially compensate for the loss of FLNA function during cortical development within PH individuals.

Original languageEnglish (US)
Pages (from-to)2845-2854
Number of pages10
JournalHuman molecular genetics
Issue number23
StatePublished - Nov 1 2002

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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