apl-1, a Caenorhabditis elegans gene encoding a protein related to the human beta-amyloid protein precursor.

Abstract

The major component of senile plaques found in the brains of Alzheimer disease patients is the 3-amyloid peptide, which is derived from a larger amyloid precursor protein (APP). Recently, a number of APP and APP-related proteins have been identified in different organisms and constitute the family of APP proteins. We have isolated several cDNAs encoding an APP-related protein in the nematode Caenorhabdiis elegans and have designated the corresponding gene as apl-i. The apl-i transcripts undergo two forms of posttranscriptional modification: trans-splicing and alternative polyadenylylation. In vitro translation of an apl-i cDNA results in a protein of approximately the expected size. Similar to the Drosophila, human, and mouse APP-related proteins, APL-1 does not appear to contain the 13-amyloid peptide. Because APP-related proteins seem to be conserved through evolution, the apl-i gene from C. elegans should be important for determining the normal function of human APP. ', where Y is T or C, N is G, A, T, or C, and R is A or G) corresponding to a highly conserved cytoplasmic region between APP and APP-related proteins. Prehybridization and hybridization were carried out at 37°C. Filters were washed at 40°C and exposed to film using intensifying screens at -700C.Positive clones were isolated and excised from the AZAP vector according to the manufacturer's protocol (Stratagene) to yield pBluescript plasmids. DNA sequencing using the double-stranded dideoxynucleotide method (38) identified three APP-related clones (APL3.2, -6.2, and -1.2.2). To isolate additional clones, the cDNA library was rescreened with APL3.2, which was 32P-labeled by random priming. For this second screen, prehybridization and hybridization were done at 650C in 6x standard saline citrate (SSC)/5x Denhardt's solution/1% SDS/0.05% sodium pyrophosphate/ salmon sperm DNA (100 ,ug/ml). Filters were then washed in 2x SSC/0.1% SDS/0.05% sodium pyrophosphate for 30 min at room temperature, followed by two 15-min washes at 680C in 0.lx SSC/0.1% SDS/0.05% sodium pyrophosphate. Hybridizing plaques were visualized by autoradiography. Isolated clones were excised and sequenced as described above.

Transgenic models of Alzheimer’s disease: Learning from animals

“…C. elegans also expresses an APP homolog: the amyloid precursor-like protein 1 (APL-1). 147 Both of these homologs are similar to APP throughout their length, but the A␤ regions lacks similarity to human APP. In Drosophila, overexpression of APPL or several human APP constructs (with and without mutations) causes an axonal transport phenotype similar to that seen in kinesin and dynein mutants, 148 implicating APP in axonal transport.…”

Defective Neuromuscular Synapses in Mice Lacking Amyloid Precursor Protein (APP) and APP-Like Protein 2

“…APP belongs to a family of conserved type I transmembrane proteins including Apl-1 in Caenorhabditis elegans (Daigle and Li, 1993), Appl in Drosophila (Rosen et al, 1989), and APP (Tanzi et al, 1987), APP-like protein 1 (APLP1) (Wasco et al, 1992), and APLP2 (Wasco et al, 1993;Slunt et al, 1994) in mammals. Within the nervous system, APP can be detected on the membranes of synaptic preparations (Kirazov et al, 2001) and has been shown to localize to the postsynaptic densities, axons, and dendrites (Schubert et al, 1991;Shigematsu et al, 1992).…”

Role of Presenilin in Mitochondrial Oxidative Stress and Neurodegeneration in <em>Caenorhabditis elegans</em>

“…The C. elegans homolog of APP, APL-1 lacks Aβ peptide sequences and β-secretase recognition sites which renders them incapable of producing amyloid peptides and hence plaques (Daigle and Li, 1993;McColl et al, 2012). Also, Aβ peptides have never been detected in C. elegans (McColl et al, 2012).…”