Deleting the phosphorylated tail domain of the neurofilament heavy subunit does not alter neurofilament transport rate in vivo.
Phosphorylation of the carboxyl tail domains of the neurofilament heavy (NF-H) and middle molecular weight (NF-M) subunits has been proposed to regulate the axonal transport of neurofilaments. To test this hypothesis, we recently constructed mice lacking the extensively phosphorylated NF-H tail domain (NF-HtailDelta) and showed that the transport rate of neurofilaments in optic axons is unaltered in the absence of this domain [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, D.W. Cleveland, 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. 158 (2002) 681-693]. However, Shea et al. proposed that deletion of NF-H carboxyl-terminal region accelerates the transport of a subpopulation of neurofilaments based on minor differences between tail-deleted and control mice in our axonal transport analysis. Here, we present additional evidence that neurofilament transport rate is unchanged after deleting the phosphorylated NF-H tail domain, establishing unequivocally that the NF-H tail domain alone does not regulate the rate of neurofilament transport in optic axons in vivo. Possible roles for tail domains as cross-bridges between a neurofilament and its neighbors or other cytoskeletal elements is discussed.
Yuan
Aidong
A
Center for Dementia Research, Nathan Kline Institute, New York University School of Medicine, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA.
Nixon
Ralph A
RA
Rao
Mala V
MV
D000818:Animals; D001370:Axonal Transport / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016900:Neurofilament Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism; D013460:Sulfur Isotopes / Q000378:metabolism; D013997:Time Factors
D016900:Neurofilament Proteins; D021122:Protein Subunits; D013460:Sulfur Isotopes; C051774:neurofilament protein H; D008715:Methionine