 |
 Previous Article | Next Article 
Journal of Neuroscience, Vol 7, 1145-1158, Copyright © 1987 by Society for Neuroscience
Posttranslational modification of neurofilament proteins by phosphate during axoplasmic transport in retinal ganglion cell neurons
RA Nixon, SE Lewis and CA Marotta
The progressive modification of newly synthesized neurofilament proteins
(NFPs) during axoplasmic transport in mouse retinal ganglion cell (RGC)
neurons was studied after RGC perikarya were pulse-labeled with
32P-orthophosphate or radiolabeled amino acids. The 3 NFP subunits, H(igh),
M(iddle), and L(ow), were among a group of axonally transported proteins
that incorporated high levels of 32P. Covalent addition of phosphate slowed
the electrophoretic mobility of H and M on SDS polyacrylamide gels and
shifted the charge of all 3 subunits toward more acidic pH values, thereby
providing an index of the phosphorylation state of this radiolabeled
population of NFPs. NFPs were extensively phosphorylated before they
entered axons at the optic nerve level, and continued to be modified during
transport along RGC axons at the optic nerve and tract level. H and M
exhibited charge shifts of 0.2-0.6 units toward a more acidic pH during
axoplasmic transport. The charge modifications became more prominent when
NFPs reached distal axonal levels, which may indicate regional differences
in the activity of this modification process along axons. By contrast, the
L subunit became more basic in charge, consistent with decreases in the
phosphorylation state during transport. Additional observations (Nixon and
Lewis, 1986) that a considerable proportion of phosphate groups initially
added to L and M were later removed as neurofilaments advanced along RGC
axons support the notion that the changing phosphorylation state of NFP
subunits during axoplasmic transport reflects a dynamic equilibrium between
phosphorylation and dephosphorylation events. Topographical remodeling of
phosphate groups on NFPs during axoplasmic transport is proposed as a
possible mechanism for coordinating interactions between neurofilaments and
other constituents, as these elements are transported and integrated into
the axonal cytoskeleton.
This article has been cited by other articles:
|
|
|
|
 
P. Rudrabhatla, W. Albers, and H. C. Pant
Peptidyl-Prolyl Isomerase 1 Regulates Protein Phosphatase 2A-Mediated Topographic Phosphorylation of Neurofilament Proteins
J. Neurosci.,
November 25, 2009;
29(47):
14869 - 14880.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Grant, Y. Zheng, and H. C. Pant
Squid (Loligo pealei) Giant Fiber System: A Model for Studying Neurodegeneration and Dementia?
Biol. Bull.,
June 1, 2006;
210(3):
318 - 333.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. V. Rao, J. Campbell, A. Yuan, A. Kumar, T. Gotow, Y. Uchiyama, and R. A. Nixon
The neurofilament middle molecular mass subunit carboxyl-terminal tail domains is essential for the radial growth and cytoskeletal architecture of axons but not for regulating neurofilament transport rate
J. Cell Biol.,
December 8, 2003;
163(5):
1021 - 1031.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. T. Helfand, P. Loomis, M. Yoon, and R. D. Goldman
Rapid transport of neural intermediate filament protein
J. Cell Sci.,
June 1, 2003;
116(11):
2345 - 2359.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. V. Rao, M. L. Garcia, Y. Miyazaki, T. Gotow, A. Yuan, S. Mattina, C. M. Ward, N. A. Calcutt, Y. Uchiyama, R. A. Nixon, et al.
Gene replacement in mice reveals that the heavily phosphorylated tail of neurofilament heavy subunit does not affect axonal caliber or the transit of cargoes in slow axonal transport
J. Cell Biol.,
August 19, 2002;
158(4):
681 - 693.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B.-S. Li, L. Zhang, J. Gu, N. D. Amin, and H. C. Pant
Integrin alpha 1beta 1-Mediated Activation of Cyclin-Dependent Kinase 5 Activity Is Involved in Neurite Outgrowth and Human Neurofilament Protein H Lys-Ser-Pro Tail Domain Phosphorylation
J. Neurosci.,
August 15, 2000;
20(16):
6055 - 6062.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Hirose, T. Ishizaki, N. Watanabe, M. Uehata, O. Kranenburg, W. H. Moolenaar, F. Matsumura, M. Maekawa, H. Bito, and S. Narumiya
Molecular Dissection of the Rho-associated Protein Kinase (p160ROCK)-regulated Neurite Remodeling in Neuroblastoma N1E-115 Cells
J. Cell Biol.,
June 29, 1998;
141(7):
1625 - 1636.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Veeranna, N. D. Amin, N. G. Ahn, H. Jaffe, C. A. Winters, P. Grant, and H. C. Pant
Mitogen-Activated Protein Kinases (Erk1,2) Phosphorylate Lys-Ser-Pro (KSP) Repeats in Neurofilament Proteins NF-H and NF-M
J. Neurosci.,
June 1, 1998;
18(11):
4008 - 4021.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A Brown
Contiguous phosphorylated and non-phosphorylated domains along axonal neurofilaments
J. Cell Sci.,
January 2, 1998;
111(4):
455 - 467.
[Abstract]
[PDF]
|
|
|
|
|
|
|
T.L. Williamson, J.R. Marszalek, J.D. Vechio, L.I. Bruijn, M.K. Lee, Z. Xu, R.H. Brown Jr., and D.W. Cleveland
Neurofilaments, Radial Growth of Axons, and Mechanisms of Motor Neuron Disease
Cold Spring Harb Symp Quant Biol,
January 1, 1996;
61(0):
709 - 723.
[Abstract]
[PDF]
|
|
|
|
|
