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A role for cyclin-dependent kinase(s) in the modulation of fast anterograde axonal transport: effects defined by olomoucine and the APC tumor suppressor proteinProteins that interact with both cytoskeletal and membrane components are candidates to modulate membrane trafficking. The tumor suppressor proteins neurofibromin (NF1) and adenomatous polyposis coli (APC) both bind to microtubules and interact with membrane-associated proteins. The effects of recombinant NF1 and APC fragments on vesicle motility were evaluated by measuring fast axonal transport along microtubules in axoplasm from squid giant axons. APC4 (amino acids 1034-2844) reduced only anterograde movements, whereas APC2 (aa 1034-2130) or APC3 (aa 2130-2844) reduced both anterograde and retrograde transport. NF1 had no effect on organelle movement in either direction. Because APC contains multiple cyclin-dependent kinase (CDK) consensus phosphorylation motifs, the kinase inhibitor olomoucine was examined. At concentrations in which olomoucine is specific for cyclin-dependent kinases (5 microM), it reduced only anterograde transport, whereas anterograde and retrograde movement were both affected at concentrations at which other kinases are inhibited as well (50 microM). Both anterograde and retrograde transport also were inhibited by histone H1 and KSPXK peptides, substrates for proline-directed kinases, including CDKs. Our data suggest that CDK-like axonal kinases modulate fast anterograde transport and that other axonal kinases may be involved in modulating retrograde transport. The specific effect of APC4 on anterograde transport suggests a model in which the binding of APC to microtubules may limit the activity of axonal CDK kinase or kinases in restricted domains, thereby affecting organelle transport.
Document ID
20040172565
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Ratner, N.
(University of Cincinnati School of Medicine Cincinnati, Ohio 45267-0521, United States)
Bloom, G. S.
Brady, S. T.
Date Acquired
August 22, 2013
Publication Date
October 1, 1998
Publication Information
Publication: The Journal of neuroscience : the official journal of the Society for Neuroscience
Volume: 18
Issue: 19
ISSN: 0270-6474
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: NS28840
CONTRACT_GRANT: NS23868
CONTRACT_GRANT: NS23320
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Neuroscience

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