A dinucleotide deletion in amyloid precursor protein (APP) mRNA associatedwith sporadic Alzheimer's disease results in efficient secretion of truncated APP isoforms from neuroblastoma cell cultures
M. Hersberger et al., A dinucleotide deletion in amyloid precursor protein (APP) mRNA associatedwith sporadic Alzheimer's disease results in efficient secretion of truncated APP isoforms from neuroblastoma cell cultures, J NEUROCHEM, 76(5), 2001, pp. 1308-1314
Recently, two dinucleotide deletions were detected in the mRNA of the amylo
id precursor protein (APP) from cerebral cortex neurons of patients with sp
oradic Alzheimer's disease (AD) or Down's syndrome. These deletions resulte
d in truncation of APP, producing an APP isoform with a 38-kDa N-terminus a
nd a novel carboxyl terminus (APP+1). We investigated the subcellular local
ization and the processing of APP+1 in the neuroblastoma cell line B103. cD
NA constructs were generated encoding fusion proteins of APP+1 or full-leng
th APP with the enhanced green fluorescent protein (eGFP). In transient tra
nsfection experiments using B103 cells, the APP+1-eGFP fusion protein showe
d a reticular localization with intense staining in the Golgi complex. Unli
ke full-length APP fused to eGFP, the APP+1-eGFP fusion protein did not loc
alize to the perinuclear area or to the plasma membrane. Western blot analy
sis of cell extracts confirmed the translation of the expected fusion prote
ins. Analysis of the supernatant by western blot indicated that the APP+1-e
GFP fusion protein was efficiently secreted from B103 cells, whereas the se
creted form of full-length APP fusion protein (APPs) was hardly detectable.
Thus, both dinucleotide deletions in the APP mRNA result in truncated APP1 that is not membrane associated and is readily secreted from neurons.