scholarly journals O3-07-05: Arf6 controls rapid lysosomal transport of cell surface APP and beta-amyloid production by macropinocytosis

2013 ◽  
Vol 9 ◽  
pp. P532-P532
Author(s):  
Stephen Pasternak ◽  
Weihao Tang ◽  
Joshua Tam ◽  
Claudia Seah ◽  
Sean Cregan ◽  
...  
Keyword(s):  
Cell Surface ◽  
Beta Amyloid ◽  
Lysosomal Transport

scholarly journals Trafficking of cell surface beta-amyloid precursor protein: retrograde and transcytotic transport in cultured neurons.

1995 ◽  
Vol 129 (2) ◽  
pp. 431-442 ◽  
Author(s):  
T Yamazaki ◽  
D J Selkoe ◽  
E H Koo
Keyword(s):  
Cell Surface ◽  
Amyloid Precursor Protein ◽  
Hippocampal Neurons ◽  
Mdck Cells ◽  
Sympathetic Neurons ◽  
Senile Plaques ◽  
Indirect Evidence ◽  
Beta Amyloid ◽  
Precursor Protein ◽  
Cultured Neurons

Amyloid beta-protein (A beta), the principal constituent of senile plaques seen in Alzheimer's disease (AD), is derived by proteolysis from the beta-amyloid precursor protein (beta PP). The mechanism of A beta production in neurons, which are hypothesized to be a rich source of A beta in brain, remains to be defined. In this study, we describe a detailed localization of cell surface beta PP and its subsequent trafficking in primary cultured neurons. Full-length cell surface beta PP was present primarily on perikarya and axons, the latter with a characteristic discontinuous pattern. At growth cones, cell surface beta PP was inconsistently detected. By visualizing the distribution of beta PP monoclonal antibodies added to intact cultures, beta PP was shown to be internalized from distal axons or terminals and retrogradely transported back to perikarya in organelles which colocalized with fluid-phase endocytic markers. Retrograde transport of beta PP was shown in both hippocampal and peripheral sympathetic neurons, the latter using a compartment culture system that isolated cell bodies from distal axons and terminals. In addition, we demonstrated that beta PP from distal axons was transcytotically transported to the surface of perikarya from distal axons in sympathetic neurons. Indirect evidence of this transcytotic pathway was obtained in hippocampal neurons using antisense oligonucleotide to the kinesin heavy chain to inhibit anterograde beta PP transport. Taken together, these results demonstrate novel aspects of beta PP trafficking in neurons, including retrograde axonal transport and transcytosis. Moreover, the axonal predominance of cell surface beta PP is unexpected in view of the recent report of polarized sorting of beta PP to the basolateral domain of MDCK cells.

Trafficking of cell-surface amyloid beta-protein precursor. I. Secretion, endocytosis and recycling as detected by labeled monoclonal antibody

1996 ◽  
Vol 109 (5) ◽  
pp. 991-998 ◽  
Author(s):  
E.H. Koo ◽  
S.L. Squazzo ◽  
D.J. Selkoe ◽  
C.H. Koo
Keyword(s):  
Monoclonal Antibody ◽  
Cell Surface ◽  
Amyloid Precursor Protein ◽  
Amyloid Beta ◽  
Senile Plaques ◽  
Beta Amyloid ◽  
Precursor Protein ◽  
Secretory Product ◽  
Amyloid Beta Protein ◽  
Lysosomal Compartment

Amyloid beta-protein, the principal constituent of amyloid fibrils found in senile plaques and blood vessels in Alzheimer's disease, is constitutively produced and released into medium of cultured cells. Amyloid beta-protein is derived by proteolysis of the beta-amyloid precursor protein by unclear mechanisms. Beta-amyloid precursor protein is a transmembrane protein which can be processed to release a large secretory product or processed in the endosomal/lysosomal pathway without secretion. Previous studies have shown that from the cell surface, beta-amyloid precursor protein may be released after cleavage or internalized without cleavage, the latter in a pathway that both produces amyloid beta-protein and also targets some molecules to the lysosomal compartment. Analysis of beta-amyloid precursor protein trafficking is confounded by the concomitant secretion and internalization of molecules from the cell surface. To address this issue, we developed an assay, based on the binding of radioiodinated monoclonal antibody, to measure the release and internalization of cell surface beta-amyloid precursor protein in transfected cells. With this approach, we showed that surface beta-amyloid precursor protein is either rapidly released or internalized, such that the duration at the cell surface is very short. Approximately 30% of cell surface beta-amyloid precursor protein molecules are released. Following internalization, a fraction of molecules are recycled while the majority of molecules are rapidly sorted to the lysosomal compartment for degradation When the C terminus of beta-amyloid precursor protein is deleted, secretion is increased by approximately 2.5-fold as compared to wild-type molecules. There is concomitant decrease in internalization in these mutant molecules as well as prolongation of the resident time on the cell surface. This observation is consistent with recent evidence that signals within the cytoplasmic domain mediate beta-amyloid precursor protein internalization.

P4-389 Neuropeptides interfere and dissolve the beta-amyloid accumulation on cell surface

2004 ◽  
Vol 25 ◽  
pp. S585
Author(s):  
Tania Valdes-Gonzalez ◽  
Aiko Ono ◽  
Tatsuo Ido
Keyword(s):  
Cell Surface ◽  
Beta Amyloid ◽  
Amyloid Accumulation

scholarly journals Polarized sorting of beta-amyloid precursor protein and its proteolytic products in MDCK cells is regulated by two independent signals.

1995 ◽  
Vol 128 (4) ◽  
pp. 537-547 ◽  
Author(s):  
C Haass ◽  
E H Koo ◽  
A Capell ◽  
D B Teplow ◽  
D J Selkoe
Keyword(s):  
Amino Acids ◽  
Cell Surface ◽  
Amyloid Precursor Protein ◽  
Mdck Cells ◽  
Membrane Vesicles ◽  
Beta Amyloid ◽  
Precursor Protein ◽  
Amyloid A ◽  
Membrane Spanning ◽  
Chloride Treatment

Progressive cerebral deposition of the amyloid (A beta) beta-protein is an early and invariant feature of Alzheimer's disease. A beta is derived by proteolysis from the membrane-spanning beta-amyloid precursor protein (beta APP). beta APP is processed into various secreted products, including soluble beta APP (APPs), the 4-kD A beta peptide, and a related 3-kD peptide (p3). We analyzed the mechanisms regulating the polarized basolateral sorting of beta APP and its proteolytic derivatives in MDCK cells. Deletion of the last 32 amino acids (residues 664-695) of the beta APP cytoplasmic tail had no influence on either the constitutive approximately 90% level of basolateral sorting of surface beta APP, or the strong basolateral secretion of APPs, A beta, and p3. However, deleting the last 42 amino acids (residues 654-695) or changing tyrosine 653 to alanine altered the distribution of cell surface beta APP so that approximately 40-50% of the molecules were inserted apically. In parallel, A beta was now secreted from both surfaces. Surprisingly, this change in surface beta APP had no influence on the basolateral secretion of APPs and p3. This result suggests that most beta APP molecules which give rise to APPs in MDCK cells are cleaved intracellularly before reaching the surface. Consistent with this conclusion, we readily detected intracellular APPs in carbonate extracts of isolated membrane vesicles. Moreover, ammonium chloride treatment resulted in the equal secretion of APPs into both compartments, as occurs with other non-membranous, basolaterally secreted proteins, but it did not influence the polarity of cell surface beta APP. These results demonstrate that in epithelial cells two independent mechanisms mediate the polarized trafficking of beta APP holoprotein and its major secreted derivative (APPs) and that A beta peptides are derived in part from beta APP holoprotein targeted to the cell surface by a signal that includes tyrosine 653.

Influence of Calcium Ions on the Plant Cell Surface: Membrane Fusions and Conformational Changes

1974 ◽  
Vol 32 ◽  
pp. 154-155
Author(s):  
D. James Morré ◽  
Charles E. Bracker ◽  
William J. VanDerWoude
Keyword(s):  
Cell Wall ◽  
Cell Surface ◽  
Conformational Changes ◽  
Calcium Ions ◽  
Surface Membrane ◽  
Carboxyl Groups ◽  
Cross Linking ◽  
Ultrastructural Evidence ◽  
Glycine Max L ◽  
Wall Extensibility

Calcium ions in the concentration range 5-100 mM inhibit auxin-induced cell elongation and wall extensibility of plant stems. Inhibition of wall extensibility requires that the tissue be living; growth inhibition cannot be explained on the basis of cross-linking of carboxyl groups of cell wall uronides by calcium ions. In this study, ultrastructural evidence was sought for an interaction of calcium ions with some component other than the wall at the cell surface of soybean (Glycine max (L.) Merr.) hypocotyls.

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