the c-terminal domains of nf-h and nf-m subunits maintain axonal neurofilament content by blocking turnover of the stationary neurofilament networknf-h和nf-m c端域的子单元维护固定的轴突神经丝的内容通过阻断营业额神经丝网络.pdf

The C-Terminal Domains of NF-H and NF-M Subunits Maintain Axonal Neurofilament Content by Blocking Turnover of the Stationary Neurofilament Network 1,2 1,2 1 1,4 1,2,3 Mala V. Rao *, Aidong Yuan , Jabbar Campbell , Asok Kumar , Ralph A. Nixon 1 Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York, United States of America, 2 Department of Psychiatry, New York University Langone Medical Center, New York, New York, United States of America, 3 Department of Cell Biology, New York University Langone Medical Center, New York, New York, United States of America, 4 Department of Pathology, New York University Langone Medical Center, New York, New York, United States of America Abstract 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)tailD] 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)tailD mice. Faster NF disappearance was accompanied by elevated levels of NF-L proteolytic fragments in NF-(H/M)tailD axons. We conclude that NF-H and NF-M C- terminal domains do not n