DOI: 10.1002/jnr.490370307. Amyloid precursor protein is enriched in axolemma and periaxolemmal‐myelin and associated clathrin‐coated vesicles

Amyloid precursor protein is enriched in axolemma and periaxolemmal‐myelin and associated clathrin‐coated vesicles

10.1002/jnr.490370307

Crossref journal-article

Wiley

Journal of Neuroscience Research (311)

Abstract

AbstractThe amyloid precursor protein (APP) is widely distributed within the CNS, where it is expressed in both neurons and glia. We have isolated axolemma and periaxolemmal‐myelin from rat brain and have determined by Western blot that APPs, Mr 100–110 kDa, are major constituents of these membrane. Isolation of axolemma, periaxolemmal‐myelin, and compact myelin show that while APP represents 1 and 0.6% of the proteins of these respective membranes, it is absent from compact myelin. These results indicate that APP transported down the axon is deposited at sites in the axolemma as well as the synapse, and that within the myelin complex, APP is targeted to the periaxolemmal domain. Both axolemma and periaxolemmal‐myelin contained a 10.5 kDa APP peptide which, based on reactivity with anti‐C‐terminal APP antibodies but not with anti‐N‐terminal antibody, appears to be a membrane‐associated C‐terminal fragment. Western blots with antibodies to Alzheimer precursor‐like proteins (APLP) indicate that APP immune reactivity is not a result of cross reactivity with APLPs. Isolation of axolemma from human autopsy material showed nearly identical results with a clear enrichment, relative to homogenate, of APP Mr 100–100 and the 10.5 kDa C‐terminal peptide. The demonstration of APP in axolemma and periaxolemmal‐myelin was replicated in membrane isolated from bovine brain. Bovine studies were extended to analysis of white matter clathrin‐coated vesicles; these data show that coated vesicles isolated from white matter, under conditions that previous studies indicate are largely endocytic vesicles, contain levels of APP comparable to that found in axolemma and periaxolemmal‐myelin. In addition, these vesicles contain cysteinly and aspartyl proteases. Incubation of axolemma with cathepsin B at pH 6.0 caused a rapid loss in the immune reactivity of APP Mr 100–110 and Mr 10.5 when analyzed with antibodies to APP672–695. This appears to be the result of hydrolysis within the epitope and not proteolysis of APP or the C‐terminal peptide, since no loss of reactivity was observed when analyzed with antibodies to sites more distal to the C‐terminus. Thus, cathepsin B hydrolyses membrane bound APP close to the C‐terminus and may be a useful tool for altering C‐terminal APP function. © 1994 Wiley‐Liss, Inc.

Bibliography

Sapirstein, V. S., Durrie, R., Berg, M. J., & Marks, N. (1994). Amyloid precursor protein is enriched in axolemma and periaxolemmalâmyelin and associated clathrinâcoated vesicles. Journal of Neuroscience Research, 37(3), 348â358. Portico.

Authors 4

V. S. Sapirstein (first)
R. Durrie (additional)
M. J. Berg (additional)
N. Marks (additional)

References 49 Referenced 23

10.1073/pnas.90.2.567
10.1073/pnas.82.19.6706
{'key': 'e_1_2_1_4_1', 'first-page': '163', 'volume-title': 'Advanced Cell Biology', 'author': 'Boehme DH', 'year': '1981'} / Advanced Cell Biology by Boehme DH (1981)
10.1016/0003-2697(76)90527-3
10.1016/0197-4580(92)90065-6
10.1016/S0021-9258(19)39742-X
10.1002/jnr.490170108
10.1016/0306-4522(92)90265-4
10.1126/science.2111583
10.1016/S0021-9258(17)42683-4 / J Biol Chem / Two developmentally regulated messenger RNAs differing in their coding region may exist for the myelin‐associated glycoprotein by Frail DE (1984)
10.1126/science.1738847
10.1523/JNEUROSCI.11-12-03783.1991 / J Neurosci / Processing of β‐amyloid precursor protein in mciro‐glia and astrocytes favors an internal localization over constitutive secretion by Haas C (1991)
10.1038/357500a0
10.1016/0165-6147(91)90609-V
10.1016/0006-8993(90)91072-O
10.1038/325733a0
10.1042/bj2310201
10.1016/S0021-9258(20)89642-2 / J Biol Chem / Isolation of baculovirus‐derived secreted and full‐length beta‐amyloid precursor protein by Knops J (1991)
10.1126/science.1589757
{'key': 'e_1_2_1_21_1', 'first-page': '561', 'article-title': 'Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport', 'volume': '87', 'author': 'Koo EH', 'year': '1990', 'journal-title': 'Proc Natl Acad Sci USA'} / Proc Natl Acad Sci USA / Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport by Koo EH (1990)
10.1038/227680a0
{'key': 'e_1_2_1_23_1', 'first-page': '1437', 'article-title': 'Localization of beta amyloid precursor protein in the rat CNS', 'volume': '18', 'author': 'Lo ACY', 'year': '1992', 'journal-title': 'Proc Soc Neurosci'} / Proc Soc Neurosci / Localization of beta amyloid precursor protein in the rat CNS by Lo ACY (1992)
10.1016/0003-9861(87)90478-4
{'key': 'e_1_2_1_25_1', 'first-page': '571', 'article-title': 'Fragmentation of Alzheimer precursor protein by brain cathepsin B and metalloendoprotease (E. C. 24.11)', 'volume': '61', 'author': 'Marks N', 'year': '1993', 'journal-title': 'J Neurochem'} / J Neurochem / Fragmentation of Alzheimer precursor protein by brain cathepsin B and metalloendoprotease (E. C. 24.11) by Marks N (1993)
{'key': 'e_1_2_1_26_1', 'first-page': '1253', 'article-title': 'Widespread expression of amyloid beta protein precursor gene in rat brain', 'volume': '134', 'author': 'Mita S', 'year': '1989', 'journal-title': 'Am J Pathol'} / Am J Pathol / Widespread expression of amyloid beta protein precursor gene in rat brain by Mita S (1989)
10.1002/jnr.490320105
10.1111/j.1471-4159.1993.tb02147.x
10.1038/362075a0
10.1016/S0021-9258(18)54194-6
10.1159/000145869
10.1007/BF00218650
10.1016/0006-291X(92)90269-Q
10.1016/S0021-9258(18)92997-2 / J Biol Chem / Purification and tissue level of the β‐amyloid peptide precursor or rat brain by Potemska FA (1991)
10.1002/jnr.490330216
10.1002/jnr.490320415
10.1111/j.1471-4159.1992.tb11352.x
10.1002/jnr.490350110
10.1016/0003-2697(87)90587-2
10.1016/0006-8993(91)91532-6
10.1016/0006-8993(92)91697-D
10.1002/j.1460-2075.1988.tb02952.x
10.1016/0165-3806(88)90134-4
10.1073/pnas.89.13.6075
10.1046/j.1365-2222.1998.00312.x
10.1016/S0076-6879(81)80045-6
10.1073/pnas.76.9.4350
10.1083/jcb.109.5.2417
10.1111/j.1471-4159.1988.tb01822.x
10.1073/pnas.89.22.10758

Dates

Type	When
Created	20 years, 8 months ago (Dec. 31, 2004, 8:56 p.m.)
Deposited	1 year, 10 months ago (Oct. 24, 2023, 9:06 a.m.)
Indexed	1 year, 10 months ago (Oct. 25, 2023, 4:46 a.m.)
Issued	31 years, 6 months ago (Feb. 15, 1994)
Published	31 years, 6 months ago (Feb. 15, 1994)
Published Online	20 years, 10 months ago (Oct. 11, 2004)
Published Print	31 years, 6 months ago (Feb. 15, 1994)

Funders 0

None

BibTeX

@article{Sapirstein_1994, title={Amyloid precursor protein is enriched in axolemma and periaxolemmal‐myelin and associated clathrin‐coated vesicles}, volume={37}, ISSN={1097-4547}, url={http://dx.doi.org/10.1002/jnr.490370307}, DOI={10.1002/jnr.490370307}, number={3}, journal={Journal of Neuroscience Research}, publisher={Wiley}, author={Sapirstein, V. S. and Durrie, R. and Berg, M. J. and Marks, N.}, year={1994}, month=feb, pages={348–358} }

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  "container-title-short": "J of Neuroscience Research",
  "published": {
    "date-parts": [
      [
        1994,
        2,
        15
      ]
    ]
  }
}