Role of Phosphorylation of Alzheimer’s Amyloid Precursor Protein during Neuronal Differentiation
- Kanae Ando1,
- Masaki Oishi2,
- Shizu Takeda1,3,
- Ko-ichi Iijima1,
- Toshio Isohara2,4,
- Angus C. Nairn2,
- Yutaka Kirino1,
- Paul Greengard2, and
- Toshiharu Suzuki1
- 1Laboratory of Neurobiophysics, School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033 Japan,
- 2Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York, 10021,
- 3Bio-oriented Technology Research Advancement Institution, Toranomon 3-18-19, Minato-ku, Tokyo 105-0001, Japan, and
- 4Life Science Research Center, Advanced Technology Research Laboratories, Nippon Steel Corporation, 3-35-1 Ida, Nakahara-ku, Kawasaki 211-0035, Japan
Abstract
Alzheimer’s amyloid precursor protein (APP), the precursor of β-amyloid (Aβ), is an integral membrane protein with a receptor-like structure. We recently demonstrated that the mature APP (mAPP; N- and O-glycosylated form) is phosphorylated at Thr668 (numbering for APP695 isoform), specifically in neurons. Phosphorylation of mAPP appears to occur during, and after, neuronal differentiation. Here we report that the phosphorylation of mAPP begins 48–72 hr after treatment of PC12 cells with NGF and that this correlates with the timing of neurite outgrowth. The phosphorylated form of APP is distributed in neurites and mostly in the growth cones of differentiating PC12 cells. PC12 cells stably expressing APP with Thr668Glu substitution showed remarkably reduced neurite extension after treatment with NGF. These observations suggest that the phosphorylated form of APP may play an important role in neurite outgrowth of differentiating neurons.
- Alzheimer’s disease
- amyloid precursor protein
- neurite outgrowth
- protein phosphorylation
- PC12 cells
- neuronal differentiation
- Received December 8, 1998.
- Revision received March 10, 1999.
- Accepted March 11, 1999.
- Copyright © 1999 Society for Neuroscience
