|Does neurofilament phosphorylation regulate axonal transport?|
Shea, Thomas B, et al.
Trends Neurosci., 26: 397-400 (2003)
Phosphorylation of neurofilaments has long been considered to regulate their axonal transport rate and, in doing so, to provide stability to mature axons. Interpretation of data recently obtained following C-terminal deletion experiments has prompted a challenge to this hypothesis. We present evidence that these deletion studies remain consistent with, rather than refute, a role for C-terminal phosphorylation in regulation of neurofilament axonal transport.
|Kinesin, dynein and neurofilament transport.|
Shea, T B and Flanagan, L A
Trends Neurosci., 24: 644-8 (2001)
The recent demonstration that the fast axonal transport motors kinesin and dynein participate in axonal transport of neurofilaments--known to undergo slow transport--supports and extends recent studies indicating that some neurofilaments exhibit alternating bursts of fast axonal transport interspersed with periods of non-motility. In addition, these findings unify both certain aspects of axonal transport and neurofilament biology. We discuss these data herein in the context of both older and more recent studies of neurofilament dynamics.
|Neurofilament protein synthesis and phosphorylation.|
Grant, P and Pant, H C
J. Neurocytol., 29: 843-72 (2000)
Neurofilament proteins, a major intermediate filament component of the neuronal cytoskeleton, are organized as 10 nm thick filaments in axons and dendrites. They are large, abundantly phosphorylated proteins with numerous phosphate acceptor sites, up to 100 in some cases, organized as numerous repeat motifs. Together with other cytoskeletal components such as microtubules, MAPs, actin and plectin-like linking molecules, they make up a dynamic lattice that sustains neuronal function from neuronal "birthday" to apoptotic cell death. The activity of the neuronal cytoskeleton is regulated by phosphorylation, dephosphorylation reactions mediated by numerous associated kinases, phosphatases and their regulators. Factors regulating multisite phosphorylation of NFs are topographically localized, with maximum phosphorylation of NF proteins consigned to axons. Phosphorylation defines the nature of NF interactions with one another and with other cytoskeletal components such as microtubules, MAPs and actin. To understand how these functional interactions are regulated by phosphorylation we attempt to identify the relevant kinases and phosphatases, their specific targets and the factors modulating their activity. As an initial working model we propose that NF phosphorylation is regulated topographically in neurons by compartment-specific macromolecular complexes of substrates, kinases and phosphatases. This implies that axonal complexes differ structurally and functionally from those in cell bodies and dendrites. Such protein assemblies, by virtue of conformational changes within proteins, facilitate ordered, sequential multisite phosphorylations that modulate dynamic cytoskeletal interactions.