Journal article
Protein serine/threonine phosphatase 1 and 2A associate with and dephosphorylate neurofilaments
Brain research. Molecular brain research, Vol.49(1), pp.15-28
1997
DOI: 10.1016/S0169-328X(97)00117-4
PMID: 9387859
Abstract
The phosphorylation state of neurofilaments plays an important role in the control of cytoskeletal integrity, axonal transport, and axon diameter. Immunocytochemical analyses of spinal cord revealed axonal localization of all protein phosphatase subunits. To determine whether protein phosphatases associate with axonal neurofilaments, neurofilament proteins were isolated from bovine spinal cord white matter by gel filtration. ≈15% of the total phosphorylase
a phosphatase activity was present in the neurofilament fraction. The catalytic subunits of PP1 and PP2A, as well as the A and B
α regulatory subunits of PP2A, were detected in the neurofilament fraction by immunoblotting, whereas PP2B and PP2C were found exclusively in the low molecular weight soluble fractions. PP1 and PP2A subunits could be partially dissociated from neurofilaments by high salt but not by phosphatase inhibitors, indicating that the interaction does not involve the catalytic site. In both neurofilament and soluble fractions, 75% of the phosphatase activity towards exogenous phosphorylase
a could be attributed to PP2A, and the remainder to PP1 as shown with specific inhibitors. Neurofilament proteins were phosphorylated in vitro by associated protein kinases which appeared to include protein kinase A, calcium/calmodulin-dependent protein kinase, and heparin-sensitive and -insensitive cofactor-independent kinases. Dephosphorylation of phosphorylated neurofilament subunits was mainly (60%) catalyzed by associated PP2A, with PP1 contributing minor activity (10–20%). These studies suggest that neurofilament-associated PP1 and PP2A play an important role in the regulation of neurofilament phosphorylation.
Details
- Title: Subtitle
- Protein serine/threonine phosphatase 1 and 2A associate with and dephosphorylate neurofilaments
- Creators
- Stefan Strack - Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232-0615, USARyan S Westphal - Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-6600, USARoger J Colbran - Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232-0615, USAFord F Ebner - Institute for Developmental Neuroscience, Vanderbilt University, Nashville, TN 37203-0040, USABrian E Wadzinski - Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-6600, USA
- Resource Type
- Journal article
- Publication Details
- Brain research. Molecular brain research, Vol.49(1), pp.15-28
- Publisher
- Elsevier B.V
- DOI
- 10.1016/S0169-328X(97)00117-4
- PMID
- 9387859
- ISSN
- 0169-328X
- eISSN
- 1872-6941
- Language
- English
- Date published
- 1997
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984040544002771
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