Topographic Regulation of Neuronal Intermediate Filaments by Phosphorylation, Role of Peptidyl-prolyl Isomerase 1: Significance in Neurodegeneration

Overview

Journal Histochem Cell Biol

Publisher Springer

Specialties Biochemistry
Cell Biology

Date 2013 Jun 25

PMID 23793952

Citations 10

Authors

B K Binukumar

Varsha Shukla

Niranjana D Amin

Preethi Reddy

Suzanne Skuntz

Philip Grant

Harish C Pant

Affiliations

Soon will be listed here.

Abstract

The neuronal cytoskeleton is tightly regulated by phosphorylation and dephosphorylation reactions mediated by numerous associated kinases, phosphatases and their regulators. Defects in the relative kinase and phosphatase activities and/or deregulation of compartment-specific phosphorylation result in neurodegenerative disorders. The largest family of cytoskeletal proteins in mammalian cells is the superfamily of intermediate filaments (IFs). The neurofilament (NF) proteins are the major IFs. Aggregated forms of hyperphosphorylated tau and phosphorylated NFs are found in pathological cell body accumulations in the central nervous system of patients suffering from Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis. The precise mechanisms for this compartment-specific phosphorylation of cytoskeletal proteins are not completely understood. In this review, we focus on the mechanisms of neurofilament phosphorylation in normal physiology and neurodegenerative diseases. We also address the recent breakthroughs in our understanding the role of different kinases and phosphatases involved in regulating the phosphorylation status of the NFs. In addition, special emphasis has been given to describe the role of phosphatases and Pin1 in phosphorylation of NFs.

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