Harish C. Pant, Ph.D.
Neuronal Cytoskeletal Protein Regulation Section
Building 49, Room 2A35
49 Convent Drive
Bethesda, MD 20892-4479
The major focus of this laboratory has been to study the mechanisms of topographic regulation of neuronal cytoskeletal proteins regulation by phosphorylation and neurodegeneration. In a normal physiological state, cytoskeletal proteins are phosphorylated extensively in the axonal compartment of a mature neuron. Although all the substrates, kinases, phosphatases and their regulators are synthesized in neuronal cell bodies, little or no cytoskeletal protein phosphorylation has been detected in the cell body compartment. Under a variety of neuropathological conditions, however, such as ALS, Alzheimers Disease, or Picks disease, hyperphosphorylation of these molecules has been found in abnormal aggregates within cell bodies, usually correlated with massive neuronal cell death. The mechanisms underlying these profound compartmental shifts in neuronal phosphorylation are not well understood.The normal physiological processes within neurons are controlled by signal transduction mechanisms that regulate the balance between protein kinase and protein phosphatase activities. We have shown that the most abundant and extensively phosphorylated motifs in the c-terminal domains (lys-ser-pro-, or KSP) are primarily phosphorylated by proline directed kinases, cdk5 and MAP kinases. Moreover, we have demonstrated that this phosphorylation is due to activation of the signal transduction cascade. Recently, we have focussed on the other part of this regulation, the protein phosphatases. The other project is to study the expression, regulation and role of neuronal Cdk5 in nerve cell function.Cdk5 is a unique multifunctional kinase. Unlike other cyclin-dependent kinases, it is expressed predominantly in post-mitotic neurons, its activity modulated by association with nervous system-specific propeins. Since its identification and characterization in our laboratory, we have been intensively studying its mechanisms of regulation and its role in nerve cell function.
Boumil EF, Vohnoutka R, Lee S, Pant H, Shea TB. Assembly and turnover of neurofilaments in growing axonal neurites. Biol Open. 2018;7(1).
Binukumar BK, Pelech SL, Sutter C, Shukla V, Amin ND, Grant P, Bhaskar M, Skuntz S, Steiner J, Pant HC. Profiling of p5, a 24 Amino Acid Inhibitory Peptide Derived from the CDK5 Activator, p35 CDKR1 Against 70 Protein Kinases. J Alzheimers Dis. 2016;54(2):525-33.
Binukumar BK, Pant HC. TFP5/TP5 peptide provides neuroprotection in the MPTP model of Parkinson's disease. Neural Regen Res. 2016;11(5):698-701.
Cardone A, Brady M, Sriram R, Pant HC, Hassan SA. Computational study of the inhibitory mechanism of the kinase CDK5 hyperactivity by peptide p5 and derivation of a pharmacophore. J Comput Aided Mol Des. 2016;30(6):513-21.
Binukumar BK, Shukla V, Amin ND, Grant P, Bhaskar M, Skuntz S, Steiner J, Pant HC. Peptide TFP5/TP5 derived from Cdk5 activator P35 provides neuroprotection in the MPTP model of Parkinson's disease. Mol Biol Cell. 2015;26(24):4478-91.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
This page was last updated on August 30th, 2018