The amino-terminal region of amyloid precursor protein is responsible for neurite outgrowth in rat neocortical explant culture.
We have previously shown that secreted forms of beta-amyloid precursor protein (APP(s)s) promote neurite outgrowth in embryonic rat neocortical explant culture. To determine the region of APP(s) responsible for its biological activity, we produced both amino- and carboxyl-terminal regions of APP(s) using a yeast expression system. The purified fragment corresponding to the amino-terminal region (NAPP) enhanced neurite outgrowth of neocortical explants, but the carboxyl-terminal region fragment did not. The neurite-promoting activity of full length APP(s) and NAPP was blocked by the antibody, 22C11, specific for the amino-terminal region, and the 16-mer peptide of epitope for 22C11 also enhanced neurite outgrowth. However, the 17-mer peptide which contains RERMS sequence did not enhance the neurite outgrowth, but promoted the survival of neocortical neurons in dissociated culture. These findings suggested that the amino-terminal region is responsible for the neurite-promoting activity of APP(s)s.
Ohsawa
I
I
Department of Neurochemistry, National Institute of Neuroscience, Kodaira, Tokyo, Japan.
Takamura
C
C
Kohsaka
S
S
D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D002540:Cerebral Cortex / Q000196:embryology / Q000502:physiology*; D005260:Female; D006801:Humans; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D011247:Pregnancy; D051381:Rats
D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments