Expression of the APP gene family in brain cells, brain development and aging.
The Alzheimer's beta A4-amyloid protein precursor (APP) and the APP-like proteins (APLPs) are transmembrane glycoproteins with a similar modular domain structure. Alternatively spliced exons found in both genes comprise a Kunitz protease inhibitor domain encoding exon, and another exon within the divergent regions adjacent to the transmembrane domain, i.e. exon 15 of the APP gene and an exon encoding 12 residues in APLP2. Omission of the latter exons in L-APP and L-APLP2 isoforms, respectively, generates a functional recognition sequence for xylosyltransferase-mediated addition of glycosaminoglycans and proteoglycan formation. In this paper, we summarize our analyses of the regulated expression of these alternatively spliced exons in APP and APLP2 in primary cultured rat brain cells, rat brain development and aging. In conjunction with additional data for the human brain, these data provide important clues for understanding the functional significance of alternative splicing and glycosylation in APP biology. On the basis of recent results showing a higher amyloidogenicity of exon 15 encoding APP than L-APP isoforms, we further discuss the potential significance of the low levels of L-APP in neurons for the susceptibility of the brain towards Alzheimer's disease.
Sandbrink
R
R
Center for Molecular Biology Heidelberg (ZMBH), University of Heidelberg, Germany.
Mönning
U
U
Masters
C L
CL
Beyreuther
K
K
D000375:Aging / Q000235:genetics*; D017398:Alternative Splicing / Q000502:physiology; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D002478:Cells, Cultured / Q000737:chemistry / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology; D015870:Gene Expression / Q000502:physiology; D006031:Glycosylation; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007536:Isomerism; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D009457:Neuroglia / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012686:Septal Nuclei / Q000166:cytology
C489697:APLP1 protein, human; C084104:APLP2 protein, human; D016564:Amyloid beta-Protein Precursor; C498283:Aplp2 protein, rat; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger