Interaction of presenilins with the filamin family of actin-binding proteins

Wanjiang Zhang, Sang Woo Han, Daniel W. McKeel, Alison Goate, Jane Y. Wu

Research output: Contribution to journalArticlepeer-review

118 Scopus citations


Mutations in presenilin genes PS1 and PS2 account for ~50% of early- onset familial Alzheimer's disease (FAD). The PS1 and PS2 genes encode highly homologous transmembrane proteins related to the Caenorhabditis elegans sel- 12 and spe-4 gene products. A hydrophilic loop region facing the cytoplasmic compartment is likely to be functionally important because at least 14 mutations in FAD patients have been identified in this region. We report here that the loop regions of PS1 and PS2 interact with nonmuscle filamin (actin- binding protein 280, ABP280) and a structurally related protein (filamin homolog 1, Fh1). Overexpression of PS1 appears to modify the distribution of ABP280 and Fh1 proteins in cultured cells. A monoclonal antibody recognizing ABP280 and Fh1 binds to blood vessels, astrocytes, neurofibrillary tangles, neuropil threads, and dystrophic neurites in the AD brain. Detection of ABP280/Fh1 proteins in these structures suggests that these presenilin- interacting proteins may be involved in the development of AD and that interactions between presenilins and ABP280/Fh1 may be functionally significant. The ABP280 gene is located on the human X chromosome, whereas the newly identified Fh1 gene maps to human chromosome 3. These results provide a new basis for understanding the function of presenilin proteins and further implicate cytoskeletal elements in AD pathogenesis.

Original languageEnglish
Pages (from-to)914-922
Number of pages9
JournalJournal of Neuroscience
Issue number3
StatePublished - 1998
Externally publishedYes


  • Actin- binding protein 280
  • Alzheimer's disease
  • Cytoskeletal elements
  • Filamin homolog 1
  • Presenilins
  • Protein-protein interaction


Dive into the research topics of 'Interaction of presenilins with the filamin family of actin-binding proteins'. Together they form a unique fingerprint.

Cite this