Expression and characterization of the Drosophila X11-like/Mint protein during neural development.
The X11-like (X11L) protein was originally isolated as a protein bound to the cytoplasmic domain of the beta-amyloid precursor protein (APP), which is associated with Alzheimer's disease. In mammals, X11L is believed to play an important role in the regulation of APP metabolism. Here we isolated and characterized the Drosophila X11L (dX11L) protein, also may be referred to this protein as Drosophila Mint (dMint), Lin 10 (dLin10) or X11 (dX11), is thought to be expressed in neuronal tissues from late embryonic through to the adult stages of the fly. The phosphotyrosine interaction domain of dX11L interacts with the cytoplasmic domain of the Drosophila amyloid precursor protein-like (APPL) similar to the way human X11L (hX11L) interacts with APP. Overexpression of dX11L on post-mitotic neurons had a lethal effect on flies and, when it was localized to the eye imaginal disc, disruption of compound eye morphology due to enhanced apoptosis of neuronal cells was observed. Overexpression of hX11L and the PDZ domain of dX11L resulted in identical eye phenotypes. The PDZ domain is highly conserved between Drosophila and human, and appears to be responsible for this phenotype. Our findings suggest that the X11L family may be involved with the regulation of apoptosis during neural cell development and that aberrant X11L function could be contribute in this way to the neuronal degeneration observed in Alzheimer's disease.
Hase
Momoko
M
Laboratory of Neurobiophysics, School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Yagi
Yoshimasa
Y
Taru
Hidenori
H
Tomita
Susumu
S
Sumioka
Akio
A
Hori
Kazuya
K
Miyamoto
Kanako
K
Sasamura
Takeshi
T
Nakamura
Makoto
M
Matsuno
Kenji
K
Suzuki
Toshiharu
T
D000595:Amino Acid Sequence / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000502:physiology; D000818:Animals; D015815:Cell Adhesion Molecules; D002470:Cell Survival / Q000502:physiology; D003593:Cytoplasm / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology; D008969:Molecular Sequence Data; D009417:Nerve Tissue / Q000166:cytology / Q000196:embryology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D013329:Structure-Activity Relationship
D016564:Amyloid beta-Protein Precursor; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D029721:Drosophila Proteins; D009687:Nuclear Proteins; C498473:X11L protein, Drosophila