Proteolytic processing of the amyloid‐β precursor protein (APP) generates the Aβ amyloid peptide of Alzheimer's disease. The biological function of APP itself remains, however, unclear. In the current review, we study in detail the different subdomains of APP and try to assign functional significance to particular structures identified in the protein.

Binding to Golgi membranes of ADP ribosylation factor 1 (ARF1) is the first event in the initiation of COPI coat assembly. Based on binding studies, a proteinaceous receptor has been proposed to be critical for this process. We now report that p23, a member of the p24 family of Golgi‐resident transmembrane proteins, is involved in ARF1 binding to membranes. Using a cross‐link approach based on a photolabile peptide corresponding to the cytoplasmic domain of p23, the GDP form of ARF1 (ARF1‐GDP) is shown to interact with p23 whereas ARF1‐GTP has no detectable affinity to p23. The p23 binding is shown to localize specifically to a 22 amino acid C‐terminal fragment of ARF1. While a monomeric form of a non‐photolabile p23 peptide does not significantly inhibit formation of the cross‐link product, the corresponding dimeric form does compete efficiently for this interaction. Consistently, the dimeric p23 peptide strongly inhibits ARF1 binding to native Golgi membranes suggesting that an oligomeric form of p23 acts as a receptor for ARF1 before nucleotide exchange takes place.

Coat protein I (COPI)-coated transport vesicles mediate protein and lipid transport in the early secretory pathway. The basic machinery required for the formation of these transport intermediates has been elucidated based on the reconstitution of COPI-coated vesicle formation from chemically defined liposomes. In this experimental system, the coat components coatomer and GTP-bound ADPribosylation factor (ARF), as well as p23 as a membrane-bound receptor for COPI coat proteins, were shown to be both necessary and sufficient to promote COPI-coated vesicle formation. coatomer ͉ ADP-ribosylation factor ͉ ARF-GAP ͉ p24 protein family

Coatomer, the coat protein complex of COPI vesicles, is involved in the budding of these vesicles, but the underlying mechanism is unknown. Toward a better understanding of this process, the interaction between coatomer and the cytoplasmic domain of a major transmembrane protein of COPI vesicles, p23, was studied. Interaction of coatomer with this peptide domain results in a conformational change and polymerization of the complex in vitro. This changed conformation also is observed in vivo, i.e., on the surface of authentic, isolated COPI vesicles. An average of four peptides was found associated with one coatomer complex after polymerization. Based on these results, we propose a mechanism by which the induced conformational change of coatomer results in its polymerization, and thus drives formation of the bud on the Golgi membrane during biogenesis of a COPI vesicle.