title: Amyloid-β precursor protein: Multiple fragments, numerous transport routes and mechanisms.
abstract: This review provides insight into the intraneuronal transport of the Amyloid-β Precursor Protein (APP), the prototype of an extensively posttranslationally modified and proteolytically cleaved transmembrane protein. Uncovering the intricacies of APP transport proves to be a challenging endeavor of cell biology research, deserving increased priority, since APP is at the core of the pathogenic process in Alzheimer's disease. After being synthesized in the endoplasmic reticulum in the neuronal soma, APP enters the intracellular transport along the secretory, endocytic, and recycling routes. Along these routes, APP undergoes cleavage into defined sets of fragments, which themselves are transported - mostly independently - to distinct sites in neurons, where they exert their functions. We review the currently known routes and mechanisms of transport of full-length APP, and of APP fragments, commenting largely on the experimental challenges posed by studying transport of extensively cleaved proteins. The review emphasizes the interrelationships between the proteolytic and posttranslational modifications, the intracellular transport, and the functions of the APP species. A goal remaining to be addressed in the future is the incorporation of the various views on APP transport into a coherent picture. In this review, the disease context is only marginally addressed; the focus is on the basic biology of APP transport under normal conditions. As shown, the studies of APP transport uncovered numerous mechanisms of transport, some of them conventional, and others, novel, awaiting exploration.
authors.affiliation: Department of Pharmacology and Physiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07101-1709, USA. Electronic address: muresavi@njms.rutgers.edu.
authors.forename: Virgil
authors.initials: V
authors.lastname: Muresan
authors.affiliation: Department of Pharmacology and Physiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07101-1709, USA. Electronic address: muresazo@njms.rutgers.edu.
authors.forename: Zoia
authors.initials: Z
authors.lastname: Ladescu Muresan
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments
keywords: Amyloid-β Precursor Protein; Intracellular transport; Kinesin-1; Microtubule motors; Phosphorylation; Secretase cleavage