Skip to main content
SpringerLink
Log in

Distribution and Expression of Protein Kinase C Interactive Protein (PKCI/HINT1) in Mouse Central Nervous System (CNS)

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Protein kinase C interactive protein (PKCI; also known as histidine triad protein, HINT1) is a small intracellular protein widely expressed in tissues from both the peripheral and CNS. Although the structure of this protein is well characterized, the functional aspect and cellular distribution of the protein remain unknown, especially in CNS. To analyze the expression pattern of PKCI/HINT1 we used antibodies against either the whole recombinant protein or a peptide epitope of PKCI/HINT1. We find widespread of PKCI/HINT1 expression in the mouse CNS by Western blot and immunostaining. Our data indicates that PKCI/HINT1 is present broadly throughout the regions of CNS with relatively high abundance in olfactory system, cerebral cortex, hippocampus and part of thalamus, hypothalamus, midbrain, pons and medulla. On the cellular level, PKCI/HINT1 immunoreactivity is primarily located in neurons and neuronal processes. This study provides the anatomical evidence for the potential roles of PKCI/HINT1 in neuronal function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

Abbreviations

3V:

3rd ventricle

4V:

4th ventricle

7n:

Facial nerve

7N:

Facial nucleus

aca:

Anterior commissure, anterior part

Acb:

Accumbens nucleus

AHP:

Anterior hypothalamic area, posterior part

AM:

Anteromedial nucleus

AO:

Accessory olfactory bulb

cc:

Corpus callosum

Cc:

Central canal

CGPn:

Central gray of pons

Cor:

Cortex

CPu:

Caudate putamen (striatum)

CNS:

Central nervous system

DG:

Dentate gyrus

EPL:

External plexiform layer (of olfactory blub)

FrA:

Frontal association cortex

Gi:

Gigantocellular reticular nucleus

GL:

Glomerular layer (of olfactory bulb)

Gr:

Gray matter

GCL:

Granular layer (of olfactory bulb)

hc:

Hippocampal commissure

Inf coll:

Inferior colliculus

IPL:

Internal plexiform layer

LH:

Lateral hypothalamic area

LMol:

Lacunosum molecular layer (of the hippocampus)

lo:

Lateral olfactory tract

LS:

Lateral septal nucleus

LV:

Lateral ventricle

M1:

Primary motor cortex

M2:

Secondary motor cortex

Med:

Medullary

MCL:

Mitral cell layer (of olfactory bulb)

ML:

Medial mammillary nucleus, lateral part

MM:

Medial mammillary nucleus, medial part

Mol:

Molecular layer

MS:

Medial septal nucleus

Or:

Oriens layer (of the hippocampus)

Pir:

Piriform cortex

PPy:

Parapyramidal nucleus

Py:

Pyramidal cell layer (of the hippocampus)

Rad:

Stratum radiatum (of the hippocampus)

RSA:

Retrosplenial granular cortex

S:

Subiculum

S1:

Primary somatosensory cortex

S2:

Secondary somatosensory cortex

SCh:

Suprachiasmatic nucleus

Sup coll:

Superior colliculus

Tu:

Olfactory tubercle

V2M:

Secondary visual cortex

VMH:

Ventromedial hypothalamic nucleus

Wh:

White matter

References

  1. Su T, Suzui M, Wang L, Lin CS, Xing WQ, Weinstein IB (2003) Deletion of histidine triad nucleotide-binding protein 1/PKC-interacting protein in mice enhances cell growth and carcinogenesis. Proc Natl Acad Sci USA 100:7824–7829

    Article  PubMed  CAS  Google Scholar 

  2. Klein MG, Yao Y, Slosberg ED, Lima CD, Doki Y, Weinstein IB (1998) Characterization of PKCI and comparative studies with FHIT, related members of the HIT protein family. Exp Cell Res 244:26–32

    Article  PubMed  CAS  Google Scholar 

  3. Lima CD, Klein MG, Weinstein IB, Hendrickson WA (1996) Three-dimensional structure of human protein kinase C interacting protein 1, a member of the HIT family of proteins. Proc Natl Acad Sci USA 93:5357–5362

    Article  PubMed  CAS  Google Scholar 

  4. Pearson JD, DeWald DB, Mathews WR, Mozier NM, Zurcher-Neely HA, Heinrikson RL, Morris MA, McCubbin WD, McDonald JR, Fraser ED (1990) Amino acid sequence and characterization of a protein inhibitor of protein kinase C. J Biol Chem 265:4583–4591

    PubMed  CAS  Google Scholar 

  5. McDonald JR, Walsh MP (1985) Ca2+-binding proteins from bovine brain including a potent inhibitor of protein kinase C. Biochem J 232:559–567

    PubMed  CAS  Google Scholar 

  6. Fraser ED, Walsh MP (1991) The major endogenous bovine brain protein kinase C inhibitor is a heat-labile protein. FEBS Lett 294:285–289

    Article  PubMed  CAS  Google Scholar 

  7. Lima CD, Klein MG, Hendrickson WA (1997) Structure-based analysis of catalysis and substrate definition in the HIT protein family. Science 278:286–290

    Article  PubMed  CAS  Google Scholar 

  8. Lee JH, Cho ES, Kim MY, Seo YW, Kho DH, Chung IJ, Kook H, Kim NS, Ahn KY, Kim KK (2005) Suppression of progression and metastasis of established colon tumors in mice by intravenous delivery of short interfering RNA targeting KITENIN, a metastasis-enhancing protein. Cancer Res 65:8993–9003

    Article  PubMed  CAS  Google Scholar 

  9. Weiske J, Huber O (2005) The histidine triad protein Hint1 interacts with Pontin and Reptin and inhibits TCF-beta-catenin-mediated transcription. J Cell Sci 118:3117–3129

    Article  PubMed  CAS  Google Scholar 

  10. Razin E, Zhang ZC, Nechushtan H, Frenkel S, Lee YN, Arudchandran R, Rivera J (1999) Suppression of microphthalmia transcriptional activity by its association with protein kinase C-interacting protein 1 in mast cells. J Biol Chem 274:34272–34276

    Article  PubMed  CAS  Google Scholar 

  11. Korsisaari N, Makela TP (2000) Interactions of Cdk7 and Kin28 with Hint/PKCI-1 and Hnt1 histidine triad proteins. J Biol Chem 275:34837–34840

    Article  PubMed  CAS  Google Scholar 

  12. Choi EK, Rhee YH, Park HJ, Ahn SD, Shin KH, Park KK (2001) Effect of protein kinase C inhibitor (PKCI) on radiation sensitivity and c-fos transcription. Int J Radiat Oncol Biol Phys 49:397–405

    Article  PubMed  CAS  Google Scholar 

  13. Vawter MP, Crook JM, Hyde TM, Kleinman JE, Weinberger DR, Becker KG, Freed WJ (2002) Microarray analysis of gene expression in the prefrontal cortex in schizophrenia: a preliminary study. Schizophr Res 58:11–20

    Article  PubMed  Google Scholar 

  14. Vawter MP, Shannon WC, Ferran E, Matsumoto M, Overman K, Hyde TM, Weinberger DR, Bunney WE, Kleinman JE (2004) Gene expression of metabolic enzymes and a protease inhibitor in the prefrontal cortex are decreased in schizophrenia. Neurochem Res 29:1245–1255

    Article  PubMed  CAS  Google Scholar 

  15. Guang W, Wang H, Su T, Weinstein IB, Wang JB (2004) Role of mPKCI, a novel mu-opioid receptor interactive protein, in receptor desensitization, phosphorylation, and morphine-induced analgesia. Mol Pharmacol 66:1285–1292

    Article  PubMed  CAS  Google Scholar 

  16. Puche AC, Heyward P, Shipley MT (2004) Transmembrane dye labeling and immunohistochemical staining of electrophysiologically characterized single neurons. J Neurosci Methods 137:235–240

    Article  PubMed  CAS  Google Scholar 

  17. Hsu SM, Raine L, Fanger H (1981) The use of antiavidin antibody and avidin-biotin-peroxidase complex in immunoperoxidase technics. Am J Clin Pathol 75:816–821

    PubMed  CAS  Google Scholar 

  18. Paxions G, Franklin KBJ (2001) The mouse brain in stereotaxic coordinates. Academic Press, San Diego

    Google Scholar 

  19. Shipley MT, Ennis M, Puche AC (2004) Olfactory system. In: Paxinos G (ed) The rat nervous system, 3ed edn. Academic Press, San Diego, pp 923–942

    Google Scholar 

  20. Parrish-Aungst S, Shipley MT, Erdelyi F, Szabo G, Puche AC (2007) Quantitative analysis of neuronal diversity in the mouse olfactory blub. J Comp Neurol 501:825–836

    Article  PubMed  CAS  Google Scholar 

  21. FitzGerald MJT, Folan-Curran J (2002) Hypothalamus, thalamus, epithalamus. In: Clinical neuroanatomy and related neuroscince. WB Saunders, London, pp 217–229

  22. Martin JH (2003) Basal ganglia. In: Neuroanatomy text and atlas. McGraw-Hill, pp 327–329

  23. Alheid GF, de Olmos JS, Beltramino CA (1995) Amygdala and extended amygdale. In: Paxinos G (ed) The rat nervous system. Academic Press, San Diego, pp 495–560

    Google Scholar 

  24. McDonald JR, Groschel-Stewart U, Walsh MP (1987) Properties and distribution of the protein inhibitor (Mr 17,000) of protein kinase C. Biochem J 242:695–705

    PubMed  CAS  Google Scholar 

  25. Tanaka C, Saito N (1992) Localization of subspecies of protein kinase C in the mammalian central nervous system. Neurochem Int 21:499–512

    Article  PubMed  CAS  Google Scholar 

  26. Merchenthaler I, Liposits Z, Reid JJ, Wetsel WC (1993) Light and electron microscopic immunocytochemical localization of PKC delta immunoreactivity in the rat central nervous system. J Comp Neurol 336:378–399

    Article  PubMed  CAS  Google Scholar 

  27. Saito N, Itouji A, Totani Y, Osawa I, Koide H, Fujisawa N, Ogita K, Tanaka C (1993) Cellular and intracellular localization of epsilon-subspecies of protein kinase C in the rat brain; presynaptic localization of the epsilon-subspecies. Brain Res 607:241–248

    Article  PubMed  CAS  Google Scholar 

  28. Saito N, Tsujino T, Fukuda K, Tanaka C (1994) Alpha-, beta II- and gamma-subspecies of protein kinase C localized in the monkey hippocampus: pre- and post-synaptic localization of gamma-subspecies. Brain Res 656:245–256

    Article  PubMed  CAS  Google Scholar 

  29. Wang H, Friedman E (2001) Increased association of brain protein kinase C with the receptor for activated C kinase-1 (RACK1) in bipolar affective disorder. Biol Psychiatry 50:364–370

    Article  PubMed  CAS  Google Scholar 

  30. Ajit SK, Ramineni S, Edris W, Hunt RA, Hum WT, Hepler JR, Young KH (2007) RGSZ1 interacts with protein kinase C interacting protein PKCI-1 and modulates mu opioid receptor signaling. Cell Signal 19:723–730

    Article  PubMed  CAS  Google Scholar 

  31. Tempel A, Zukin RS (1987) Neuroanatomical patterns of the mu, delta, and kappa opioid receptors of rat brain as determined by quantitative in vitro autoradiography. Proc Natl Acad Sci USA 84:4308–4312

    Article  PubMed  CAS  Google Scholar 

  32. Mansour A, Fox CA, Akil H, Watson SJ (1995) Opioid-receptor mRNA expression in the rat CNS: anatomical and functional implications. Trends Neurosci 18:22–29

    Article  PubMed  CAS  Google Scholar 

  33. Moriwaki A, Wang JB, Svingos A, van Bockstaele E, Cheng P, Pickel V, Uhl GR (1996) mu Opiate receptor immunoreactivity in rat central nervous system. Neurochem Res 21:1315–1331

    Article  PubMed  CAS  Google Scholar 

  34. Lewis DA, Lieberman JA (2000) Catching up on schizophrenia: natural history and neurobiology. Neuron 28:325–334

    Article  PubMed  CAS  Google Scholar 

  35. Seeman P (1987) Dopamine receptors and the dopamine hypothesis of schizophrenia. Synapse 1:133–152

    Article  PubMed  CAS  Google Scholar 

  36. Ongali B, Ase AR, Hebert C, Amdiss F, Reader TA (2000) Dopamine D(1) and D(2) receptors in the forebrain of dystonia musculorum mutant mice: an autoradiographic survey in relation to dopamine contents. Synapse 37:1–15

    Article  PubMed  CAS  Google Scholar 

  37. Reader TA, Ase AR, Hebert C, Amdiss F (1999) Distribution of dopamine, its metabolites, and D1 and D2 receptors in heterozygous and homozygous weaver mutant mice. Neurochem Res 24:1455–1470

    Article  PubMed  CAS  Google Scholar 

  38. Barbier E, Zapata A, Oh E, Liu Q, Zhu F, Undie A, Shippenberg T, Wang JB (2007) Supersensitivity to amphetamine in protein kinase-C interacting protein/HINT1 knockout mice. Neuropsychopharmacology 32(8):1774–1782

    Article  PubMed  CAS  Google Scholar 

  39. Kawaguchi Y, Kondo S (2002) Parvalbumin, somatostatin and cholecystokinin as chemical markers for specific GABAergic interneuron types in the rat frontal cortex. J Neurocytol 31:277–287

    Article  PubMed  Google Scholar 

  40. Alreja M, Shanabrough M, Liu W, Leranth C (2000) Opioids suppress IPSCs in neurons of the rat medial septum/diagonal band of Broca: involvement of mu-opioid receptors and septohippocampal GABAergic neurons. J Neurosci 20:1179–1189

    PubMed  CAS  Google Scholar 

  41. McQuiston AR (2007) Effects of mu-opioid receptor modulation on GABAB receptor synaptic function in hippocampal CA1. J Neurophysiol 97:2301–2311

    Article  PubMed  CAS  Google Scholar 

  42. Steffensen SC, Stobbs SH, Colago EE, Lee RS, Koob GF, Gallegos RA, Henriksen SJ (2006) Contingent and non-contingent effects of heroin on mu-opioid receptor-containing ventral tegmental area GABA neurons. Exp Neurol 202:139–151

    Article  PubMed  CAS  Google Scholar 

  43. Svingos AL, Moriwaki A, Wang JB, Uhl GR, Pickel VM (1997) mu-Opioid receptors are localized to extrasynaptic plasma membranes of GABAergic neurons and their targets in the rat nucleus accumbens. J Neurosci 17:2585–2594

    PubMed  CAS  Google Scholar 

  44. Kalyuzhny AE, Wessendorf MW (1997) CNS GABA neurons express the mu-opioid receptor: immunocytochemical studies. Neuroreport 8:3367–3372

    Article  PubMed  CAS  Google Scholar 

  45. Kalyuzhny AE, Wessendorf MW (1998) Relationship of mu- and delta-opioid receptors to GABAergic neurons in the central nervous system, including antinociceptive brainstem circuits. J Comp Neurol 392:528–547

    Article  PubMed  CAS  Google Scholar 

  46. Stumm RK, Zhou C, Schulz S, Hollt V (2004) Neuronal types expressing mu- and delta-opioid receptor mRNA in the rat hippocampal formation. J Comp Neurol 469:107–118

    Article  PubMed  CAS  Google Scholar 

  47. Berghuis P, Dobszay MB, Ibanez RM, Ernfors P, Harkany T (2004) Turning the heterogeneous into homogeneous: studies on selectively isolated GABAergic interneuron subsets. Int J Dev Neurosci 22:533–543

    Article  PubMed  CAS  Google Scholar 

  48. Gupta A, Wang Y, Markram H (2000) Organizing principles for a diversity of GABAergic interneurons and synapses in the neocortex. Science 287:273–278

    Article  PubMed  CAS  Google Scholar 

  49. Weiske J, Huber O (2006) The histidine triad protein Hint1 triggers apoptosis independent of its enzymatic activity. J Biol Chem 281:27356–27366

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Support for this work was provided by grants from NIDA/NIH to J.B. Wang (DA11925; DA018722). We thank Dr. I.B. Weinstein from Columbia University for providing PKCI/HINT1 KO mice and anti-hPKCI/HINT1 antibody.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD, 21201, USA

    Qing Liu & Jia Bei Wang

  2. Department of Anatomy and Neuroscience, School of Medicine, University of Maryland, Baltimore, MD, USA

    Adam C. Puche

Authors
  1. Qing Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Adam C. Puche
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jia Bei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jia Bei Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, Q., Puche, A.C. & Wang, J.B. Distribution and Expression of Protein Kinase C Interactive Protein (PKCI/HINT1) in Mouse Central Nervous System (CNS). Neurochem Res 33, 1263–1276 (2008). https://doi.org/10.1007/s11064-007-9578-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-007-9578-4

Keywords

Search

Navigation