We have updated our privacy policy. If you have any question, contact us at privacy@scicrunch.org. Dismiss and don't show again

Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

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

Mutations in presenilin genes PS1 and PS2 account for approximately 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.

Pubmed ID: 9437013 RIS Download

Mesh terms: Aged | Aged, 80 and over | Alzheimer Disease | Animals | Antibodies, Monoclonal | Brain Chemistry | COS Cells | Carrier Proteins | Chromosome Mapping | Chromosomes, Human, Pair 3 | Contractile Proteins | Cytoskeleton | Female | Filamins | Humans | Male | Membrane Proteins | Microfilament Proteins | Molecular Sequence Data | Mutation | Neuropil | Presenilin-1 | Presenilin-2 | Protein Binding | Protein Structure, Tertiary | Sequence Homology, Amino Acid | Transfection | Yeasts

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NEI NIH HHS, Id: R01 EY014576-03
  • Agency: NIGMS NIH HHS, Id: R01 GM070967-02
  • Agency: NIA NIH HHS, Id: AG-05861
  • Agency: NIA NIH HHS, Id: P50 AG005681
  • Agency: NCI NIH HHS, Id: R01 CA114197-01A2
  • Agency: NIA NIH HHS, Id: AG05681
  • Agency: NIA NIH HHS, Id: AG00634
  • Agency: NEI NIH HHS, Id: R01 EY014576
  • Agency: NIGMS NIH HHS, Id: R01 GM070967
  • Agency: NIA NIH HHS, Id: F32 AG005861
  • Agency: NCI NIH HHS, Id: R01 CA114197

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.