RT Journal Article
SR Electronic
T1 Study of Proline-Directed Protein Kinases Involved in Phosphorylation of the Heavy Neurofilament Subunit
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9466
OP 9472
DO 10.1523/JNEUROSCI.17-24-09466.1997
VO 17
IS 24
A1 Benoit I. Giasson
A1 Walter E. Mushynski
YR 1997
UL http://www.jneurosci.org/content/17/24/9466.abstract
AB The high-molecular-mass neurofilament subunit (NFH) is normally hypophosphorylated in the neuronal perikaryon and undergoes extensive phosphorylation after entering the initial axon segment. Aberrant hyperphosphorylation of perikaryal NFH is a common feature of many neurological diseases. In a previous study (Giasson and Mushynski, 1996), we demonstrated a correlation between phosphorylation of perikaryal NFH and induction of stress-activated protein kinase (SAPK)-γ. In this report, we present direct evidence showing that thein vivo activation of SAPKs by an upstream activator (MEKK-1) caused extensive NFH phosphorylation. We also show that stress-activated p38 kinases were not involved in the phosphorylation of perikaryal NFH in cultured dorsal root ganglion neurons and that this process was reversible. SAPKγ was shown to be located in both the cell body and the neurites of the cultured neurons, suggesting that it is likely to be involved in the phosphorylation of cytoplasmic substrates. These could include neuritic NFH, which is highly phosphorylated despite the demonstrated lack of cyclin-dependent kinase-5 activity in these neurons. Neuritic NFH was also highly phosphorylated in neuronal cultures devoid of Schwann cells, indicating that this form of post-translational modification does not require cues stemming from Schwann cell–axon contacts. Collectively, these findings provide significant new insights into mechanisms involved in NFH phosphorylation in normal neurons and in disease states characterized by aberrant phosphorylation of neurofilaments.