Newly synthesized neurofilaments or protofilaments are incorporated into a highly stable stationary cytoskeleton network as they are transported along axons. Although the heavily phosphorylated carboxyl-terminal tail domains of the heavy and medium neurofilament (NF) subunits have been proposed to contribute to this process and particularly to stability of this structure, their function is still obscure. Here we show in NF-H/M tail deletion [NF-(H/M)(tailΔ)] mice that the deletion of both of these domains selectively lowers NF levels 3-6 fold along optic axons without altering either rates of subunit synthesis or the rate of slow axonal transport of NF. Pulse labeling studies carried out over 90 days revealed a significantly faster rate of disappearance of NF from the stationary NF network of optic axons in NF-(H/M)(tailΔ) mice. Faster NF disappearance was accompanied by elevated levels of NF-L proteolytic fragments in NF-(H/M)(tailΔ) axons. We conclude that NF-H and NF-M C-terminal domains do not normally regulate NF transport rates as previously proposed, but instead increase the proteolytic resistance of NF, thereby stabilizing the stationary neurofilament cytoskeleton along axons.
Pubmed ID: 23028520 RIS Download
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Instrument that accurately gathers participant responses and verifies signals. The Celeritas Series response units are assembled using high-impact, chemical resistant, medical grade plastic. The response units include a tactile indicator to ensure correct finger placement during experiments and comfortably attach to the participant?s wrists. The units communicate button presses through fiber optic cabling which connects to a Fiber Optic Interface Console located in the control room through an available wave guide. The interface console provides real-time feedback of participant responses via LED indicators and includes a set of switches which can be used to make responses for the participant as needed.
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