» Articles » PMID: 24845512

The Evolutionary Strata of DARPP-32 Tail Implicates Hierarchical Functional Expansion in Higher Vertebrates

Overview
Journal J Biosci
Specialties Biochemistry
Biology
Date 2014 May 22
PMID 24845512
Authors
Affiliations
Soon will be listed here.
Abstract

DARPP-32 (dopamine and adenosine 3', 5'-monophosphate-regulated phosphoprotein of 32 kDa), which belongs to PPP1R1 gene family, is known to act as an important integrator in dopamine-mediated neurotransmission via the inhibition of protein phosphatase-1 (PP1). Besides its neuronal roles, this protein also behaves as a key player in pathological and pharmacological aspects. Use of bioinformatics and phylogenetics approaches to further characterize the molecular features of DARPP-32 can guide future works. Predicted phosphorylation sites on DARPP-32 show conservation across vertebrates. Phylogenetics analysis indicates evolutionary strata of phosphorylation site acquisition at the C-terminus, suggesting functional expansion of DARPP-32, where more diverse signalling cues may involve in regulating DARPP-32 in inhibiting PP1 activity. Moreover, both phylogenetics and synteny analyses suggest de novo origination of PPP1R1 gene family via chromosomal rearrangement and exonization.

References
1.
Neyroz P, Desdouits F, Benfenati F, Knutson J, Greengard P, Girault J . Study of the conformation of DARPP-32, a dopamine- and cAMP-regulated phosphoprotein, by fluorescence spectroscopy. J Biol Chem. 1993; 268(32):24022-31. View

2.
Marsh J, Dancheck B, Ragusa M, Allaire M, Forman-Kay J, Peti W . Structural diversity in free and bound states of intrinsically disordered protein phosphatase 1 regulators. Structure. 2010; 18(9):1094-103. PMC: 2936704. DOI: 10.1016/j.str.2010.05.015. View

3.
Stipanovich A, Valjent E, Matamales M, Nishi A, Ahn J, Maroteaux M . A phosphatase cascade by which rewarding stimuli control nucleosomal response. Nature. 2008; 453(7197):879-84. PMC: 2796210. DOI: 10.1038/nature06994. View

4.
Meister B, Fryckstedt J, Schalling M, Cortes R, Hokfelt T, Aperia A . Dopamine- and cAMP-regulated phosphoprotein (DARPP-32) and dopamine DA1 agonist-sensitive Na+,K+-ATPase in renal tubule cells. Proc Natl Acad Sci U S A. 1989; 86(20):8068-72. PMC: 298216. DOI: 10.1073/pnas.86.20.8068. View

5.
Goldberg J, Huang H, Kwon Y, Greengard P, Nairn A, Kuriyan J . Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatase-1. Nature. 1995; 376(6543):745-53. DOI: 10.1038/376745a0. View