Neurofilament phosphorylation and axon diameter in the squid giant fibre system

Martin, Rainer de; Door, R.; Ziegler, Andreas; Warchoł, Wojciech; Hahn, Janina; Breitig, D.

doi:10.1016/s0306-4522(98)00244-9

Cited by 29 publications

(16 citation statements)

References 34 publications

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“…In the development of axons, NF subunits, particularly NFM and NFH, become heavily phosphorylated on these carboxy terminus side arms (Lee and Cleveland, 1996). This phosphorylation occurs simultaneously with NF transport down the axon, and is associated with both a decrease in NF transport rate and an increase in axonal caliber (Martin et al, 1999), thus rendering the phosphorylated NFH subunit an excellent marker of axonal maturity. The phosphorylation of NFH, rather than NFH expression, has been suggested to be a late event in axonal growth, and probably related to axonal maturation, thus supporting our use of phosphorylated NFH as a marker of axonal maturity (Martin et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…This phosphorylation occurs simultaneously with NF transport down the axon, and is associated with both a decrease in NF transport rate and an increase in axonal caliber (Martin et al, 1999), thus rendering the phosphorylated NFH subunit an excellent marker of axonal maturity. The phosphorylation of NFH, rather than NFH expression, has been suggested to be a late event in axonal growth, and probably related to axonal maturation, thus supporting our use of phosphorylated NFH as a marker of axonal maturity (Martin et al, 1999). In our study, phosphorylated NFH, stained with SMI 31, did not reach adult levels until 8 postnatal months (72 PC weeks), as determined by immunocytochemistry.…”

Section: Discussionmentioning

confidence: 99%

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Axonal development in the cerebral white matter of the human fetus and infant

Haynes

Borenstein

DeSilva

et al. 2005

J of Comparative Neurology

192

144

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After completion of neuronal migration to form the cerebral cortex, axons undergo rapid elongation to their intra- and subcortical targets, from midgestation through infancy. We define axonal development in the human parietal white matter in this critical period. Immunocytochemistry and Western blot analysis were performed on 46 normative cases from 20-183 postconceptional (PC) weeks. Anti-SMI 312, a pan-marker of neurofilaments, stained axons as early as 23 weeks. Anti-SMI 32, a marker for nonphosphorylated neurofilament high molecular weight (NFH), primarily stained neuronal cell bodies (cortical, subcortical, and Cajal-Retzius). Anti-SMI 31, which stains phosphorylated NFH, was used as a marker of axonal maturity, and showed relatively low levels of staining (approximately one-fourth of adult levels) from 24-34 PC weeks. GAP-43, a marker of axonal growth and elongation, showed high levels of expression in the white matter from 21-64 PC weeks and lower, adult-like levels beyond 17 postnatal months. The onset of myelination, as seen by myelin basic protein expression, was approximately 54 weeks, with progression to "adult-like" staining by 72-92 PC weeks. This study provides major insight into axonal maturation during a critical period of growth, over an age range not previously examined and one coinciding with the peak period of periventricular leukomalacia (PVL), the major disorder underlying cerebral palsy in premature infants. These data suggest that immature axons are susceptible to damage in PVL and that the timing of axonal maturation must be considered toward establishing its pathology relative to the oligodendrocyte/myelin/axonal unit.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Axonal development in the cerebral white matter of the human fetus and infant

Haynes

Borenstein

DeSilva

et al. 2005

J of Comparative Neurology

192

144

View full text Add to dashboard Cite

show abstract

“…It is conceivable that NF phosphorylation in the auditory nerve plays a critical role in the sensitivity of hearing, since growth of the axon diameter is a function of NF phosphorylation (Martin et al, 1999) and axonal caliber determines the conduction velocity of the nerve (Braissant, 2007). Furthermore, evidence is growing that NF phosphorylation also participates in synaptic regulation, possibly by tethering key kinases and/or phosphatases to their respective substrates at the post synaptic terminal (Grant and Pant, 2000), which may affect hearing.…”

Section: Discussionmentioning

confidence: 99%

Neurofilament localization and phosphorylation in the developing inner ear of the rat

2010

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“…4,5 The major phosphorylation sites correspond to the serine amino acids of Lys-Ser-Pro (KSP) repeat motifs, 4 where serine phosphorylation changes the charge of the KSP motif from + 1e to − 1e. These phosphorylation sites are particularly found in NF-H and NF-M sidearms that have varying numbers of KSP repeat motifs (43-52 repeats in rodent and human NF-H; [6][7][8][9] 12 repeats in human NF-M). 10 The phosphorylation of these KSP repeats alters the charge density of the protrusions and is considered to increase the lateral extension of sidearms 11,12 (through repulsive interactions of negatively charged sites).…”

Section: Introductionmentioning

confidence: 99%