The high and middle molecular weight neurofilament subunits regulate the association of neurofilaments with kinesin: inhibition by phosphorylation of the high molecular weight subunit.
Kinesin participates in axonal transport of neurofilaments (NFs), but the mode by which they attach to kinesin is unclear. We compared the association of NFs with kinesin in mice expressing or lacking NF-H or NF-M. In normal and M-/- mice, the leading edge of metabolically labeled NF subunits was selectively co-precipitated with kinesin. By contrast, the entire wave of radiolabeled subunits co-precipitated with kinesin in H-/- mice. Similar bulk levels of NFs co-precipitated with kinesin from normal and H-/- mice, but reduced levels co-precipitated from M-/- mice. These data suggest that both NF-H and NF-M regulate the association of NFs with kinesin. They further indicate that phosphorylation of NF-H dissociates NFs from kinesin and provides a mechanism by which NF-H phosphorylation can contribute to the slowing of NF axonal transport.
Jung
Cheolwha
C
Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, University of Massachusetts, Lowell, One University Avenue, Lowell, MA 01854, USA.
Lee
Sangmook
S
Ortiz
Daniela
D
Zhu
Qinzhang
Q
Julien
Jean-Pierre
JP
Shea
Thomas B
TB
D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D007382:Intermediate Filaments / Q000378:metabolism* / Q000648:ultrastructure; D016547:Kinesins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020409:Molecular Motor Proteins / Q000502:physiology*; D008970:Molecular Weight; D009431:Neural Conduction / Q000502:physiology; D016900:Neurofilament Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009900:Optic Nerve / Q000737:chemistry / Q000648:ultrastructure; D010766:Phosphorylation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D012165:Retinal Ganglion Cells / Q000737:chemistry / Q000648:ultrastructure
D020409:Molecular Motor Proteins; D016900:Neurofilament Proteins; C051774:neurofilament protein H; C061195:neurofilament protein M; D016547:Kinesins