A putative role for cell cycle-related proteins in microtubule-based neuroplasticity.
Cyclins and cyclin-dependent kinases (Cdks) are the main components that control the orderly progression through cell cycle. In the mature nervous system, terminally differentiated neurons are permanently withdrawn from cell cycle, as mitotic quiescence is essential for the functional stability of the complexly wired neuronal system. Recently, we characterized the expression and colocalization of cyclins and Cdks in terminally differentiated pyramidal neurons. The functional impact of the expression of cell cycle-related proteins in differentiated neurons, however, has not been elucidated yet. In the present study, we show by immunoelectron microscopy and immunobiochemical methods an association of cyclins and Cdks with the microtubule network. Cyclins D, E, A and B as well as Cdks 1, 2 and 4 were also found to be associated with the microtubule-associated protein tau. Cyclin/Cdk complexes, in addition, exhibit kinase activity towards tau. In vitro, downregulation of cyclins and Cdks by a siRNA approach and by pharmacological inhibition promotes neurite extension. Taken together, these results indicate that the expression of cell cycle-related proteins in terminal differentiated neurons is associated with physiological functions beyond cell cycle control that might be involved in microtubule-based mechanisms of neuroplasticity.
Schmetsdorf
Stefanie
S
Paul Flechsig Institute for Brain Research, Department for Molecular and Cellular Mechanisms of Neurodegeneration, University of Leipzig, Leipzig, Germany. stefanie.schmetsdorf@medizin.uni-leipzig.de
Arnold
Erik
E
Holzer
Max
M
Arendt
Thomas
T
Gärtner
Ulrich
U
D000818:Animals; D002417:Cattle; D018797:Cell Cycle Proteins / Q000145:classification / Q000378:metabolism*; D002478:Cells, Cultured; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000145:classification / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D047468:Immunoprecipitation / Q000379:methods; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016253:Microscopy, Immunoelectron / Q000379:methods; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure*; D010766:Phosphorylation / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D034741:RNA, Small Interfering / Q000378:metabolism; D013003:Somatosensory Cortex / Q000166:cytology / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014404:Tubulin / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D018797:Cell Cycle Proteins; D016213:Cyclins; D004791:Enzyme Inhibitors; D034741:RNA, Small Interfering; D014404:Tubulin; D016875:tau Proteins; D018844:Cyclin-Dependent Kinases