Presenilin affects arm/beta-catenin localization and function in Drosophila.
Presenilin is an essential gene for development that when disrupted leads to a neurogenic phenotype that closely resembles Notch loss of function in Drosophila. In humans, many naturally occurring mutations in Presenilin 1 or 2 cause early onset Alzheimer's disease. Both loss of expression and overexpression of Presenilin suggested a role for this protein in the localization of Armadillo/beta-catenin. In blastoderm stage Presenilin mutants, Arm is aberrantly distributed, often in Ubiquitin-immunoreactive cytoplasmic inclusions predominantly located basally in the cell. These inclusions were not observed in loss of function Notch mutants, suggesting that failure to process Notch is not the only consequence of the loss of Presenilin function. Human presenilin 1 expressed in Drosophila produces embryonic phenotypes resembling those associated with mutations in Armadillo and exhibited reduced Armadillo at the plasma membrane that is likely due to retention of Armadillo in a complex with Presenilin. The interaction between Armadillo/beta-catenin and Presenilin 1 requires a third protein which may be delta-catenin. Our results suggest that Presenilin may regulate the delivery of a multiprotein complex that regulates Armadillo trafficking between the adherens junction and the proteasome.
Noll
E
E
Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Medina
M
M
Hartley
D
D
Zhou
J
J
Perrimon
N
N
Kosik
K S
KS
D000818:Animals; D030801:Animals, Genetically Modified; D051186:Armadillo Domain Proteins; D051177:Catenins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D006801:Humans; D066298:In Vitro Techniques; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D010750:Phosphoproteins; D053764:Presenilin-1; D051880:Receptors, Notch; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; D000095002:Delta Catenin
C495305:ARM protein, Drosophila; D051186:Armadillo Domain Proteins; C495270:CTNNB1 protein, human; D051177:Catenins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; C508853:PSEN1 protein, human; D010750:Phosphoproteins; D053764:Presenilin-1; D051880:Receptors, Notch; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; D000095002:Delta Catenin