The single lamprey neurofilament subunit (NF-180) lacks multiphosphorylation repeats and is expressed selectively in projection neurons.
The lamprey is considered the most primitive living vertebrate and its neurofilaments (NFs) are unique in being homopolymers of a single 180 kDa subunit (NF-180). Previous immunologic studies have suggested that the sidearm of NF-180 is highly phosphorylated selectively in the largest diameter axons. We report in this study the isolation and characterization of cDNA clones encoding the NF-180 lamprey protein. In situ hybridization with digoxigenin-labeled cRNA revealed NF-180 message exclusively in neurons with long axons, such as reticulospinal neurons and cranial motor neurons. The core of NF-180 was similar in structure to those of mammalian neurofilaments, but surprisingly, the carboxy sidearm lacked the multiphosphorylation repeats characteristic of higher vertebrate and invertebrate neurofilaments. Overall there was a paucity of potential phosphorylation sites in the NF-180 carboxy-terminus compared to NF-M and NF-H of mammals, fish and squid. This, along with the highly acidic nature of the NF-180 sidearm, makes it unlikely that phosphorylation of sidearm residues regulates interfilament spacing and axon diameter through global electrostatic repulsion of the carboxy-terminus away from the filament backbone. Furthermore, the expression of a single neurofilament subunit in the lamprey that is most similar to the NF-M of higher vertebrates suggests that all three mammalian neurofilament subunits evolved from a single NF-M-like precursor.
Jacobs
A J
AJ
Department of Neurology, University of Pennsylvania Medical Center, Philadelphia 19104-4283, USA.
Kamholz
J
J
Selzer
M E
ME
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D004076:Digoxigenin; D017403:In Situ Hybridization; D007798:Lampreys / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D016900:Neurofilament Proteins / Q000235:genetics* / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D010766:Phosphorylation; D012091:Repetitive Sequences, Nucleic Acid; D009435:Synaptic Transmission; D014018:Tissue Distribution
D016900:Neurofilament Proteins; D004076:Digoxigenin