By E. Grote, F. Bonzelius, G. Herman (auth.), K. S. Kosik M.D., D. J. Selkoe M.D., Y. Christen Ph.D. (eds.)
Like the unflinching gaze of Captain Ahab strolling the deck of the Pequod, Alzheimer researchers have had their attractions mounted firmly at the illness for a few years. Now, as this quantity amply demonstrates, entire researchers from different fields, who've idea deeply approximately mobile organic difficulties are employing their insights to Alzheimer's disorder. The contri butions right here signify the textual content models of the lawsuits from the 10th "Colloque medecine et recherche" of the Fondation IPSEN dedicated to study on Alzheimer's disorder. The symposium, entitled "Alzheimer's ailment: classes from cellphone Biology" used to be held in Paris on April 25, 1994. As is clear from the numerous backgrounds of the members, the medical pursuit of Alzheimer's affliction has started to meld with extra uncomplicated disciplines, quite mobilephone biology. whereas at the one hand, new components of specialization are always rising, the bounds of older disciplines are increas ingly blurred. probably for many of the years because the first descriptions of the disorder in 1907, the technological know-how of Alzheimer's affliction used to be descriptive, and lay within the province of pathologists. this period of time, within which greatly used to be realized concerning the topography of senile plaques and neurofibrillary tangles, culminated with an ultrastructural description of those hallmark buildings. the trendy period of Alzheimer's affliction examine opened with the iden tification of the part proteins in plaques and tangles.
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Ann Rev Cell Bioi 9: 163-206 Mechanisms of Molecular Sorting in Polarized Cells: Relevance to Alzheimer's Disease l. Mellman*, K. Matter, E. Yamamoto, N. Pollack, 1. Roome, K. Feisenstein, and S. Roberts Summary The plasma membranes of many cell types, such as epithelial cell and neurons, are polarized into distinct domains. In epithelial cells, we have found, that the targeting of newly synthesized membrane proteins is governed largely by a ubiquitously distributed set of cytoplasmic domain sorting signals.
Mellman et al. et al. 1991). Interestingly, both basolateral targeting and endocytosis were often found to be dependent on critical tyrosine residues. Due to this superficial relationship between coated pit localization and basolateral targeting, we next performed a detailed analysis of the amino acid sequences involved in polarized sorting using the human LDL receptor, as the receptor's coated pit localization domain had already been extensively characterized. In fact, we found that the LDL receptor cytoplasmic domain contains not one, but two basolateral sorting signals.
Enzymes involved in hydrolysis, amino acid, and sugar transport are all found on the apical plasma membrane, which, moreover, is characterized by highly differentiated microvillar outcroppings that aid in the absorption process. In contrast, the basolateral surface contained most of the membrane proteins responsible for the constitutive or "housekeeping" functions common to all cells, polarized and non-polarized (Fig. 1). Thus, the apical surface appeared to be a privileged site, transport to which whould appear most likely to require a specific sorting signal; in the absence of this signal, basolateral transport was viewed as occurring by default.