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Gene Review

PCDH8  -  protocadherin 8

Homo sapiens

Synonyms: ARCADLIN, Arcadlin, PAPC, Protocadherin-8
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High impact information on PCDH8

  • Moreover, loss of endogenous PAPC results in elevated C-cadherin adhesion activity in the dorsal mesoderm and interferes with the normal blastopore closure, a defect that can be rescued by a dominant-negative C-cadherin mutant [1].
  • In normal cells, replacement of native PC with 1-palmitoyl,2-arachidonoyl PC (PAPC) resulted in a decrease in osmotic fragility with no change in hydration, whereas replacement with 1,2-dipalmitoyl PC (DPPC) led to an increased osmotic fragility and cellular hydration [2].
  • To analyze the gene expression changes that oxidized lipids induce in endothelial cells, we used a suppression subtractive hybridization procedure to compare mRNA from PAPC-treated human aortic endothelial cells (HAEC) with that of ox-PAPC-treated cells [3].
  • Its close homology with cadherins, its rapid inducibility by neural activity, and its involvement in synaptic transmission suggest that Arcadlin may play an important role in activity-induced synaptic reorganization underlying long term memory [4].
  • Furthermore, application of Arcadlin antibody reduces excitatory postsynaptic potential amplitude and blocks long term potentiation in hippocampal slices [4].

Biological context of PCDH8

  • Characterization of two novel protocadherins (PCDH8 and PCDH9) localized on human chromosome 13 and mouse chromosome 14 [5].
  • In this study we describe the isolation and characterization of two novel protocadherins, PCDH8 and PCDH9, that constitute a new linkage group on human chromosome 13 and mouse chromosome 14 [5].
  • In contrast to the classical and desmosomal cadherins, which in general consist of 15-17 exons and share a remarkable degree of conservation in intron position, PCDH8 consists of only three exons and lacks introns in the extracellular domain [5].
  • In this study, the entire expressed sequence of the PCDH8 gene and over 800 bp of the 5' flanking region were screened for polymorphisms in 30 DSM-IV schizophrenia individuals using Denaturing High Performance Liquid Chromatography (DHPLC) [6].
  • Human LCAT prefers phosphatidylcholine (PC) with sn-1-palmitoyl-2-oleoyl PC (POPC) as substrate for cholesteryl ester synthesis, whereas rat LCAT (which is 92% similar in amino acid sequence) prefers sn-1-palmitoyl-2-arachidonoyl PC (PAPC) [7].

Anatomical context of PCDH8

  • The initial rate of fusion increased in the order 1-palmitoyl 2-arachidonoyl PC (PAPC) > 1-palmitoyl 2-oleoyl PC (POPC) > 1-stearoyl 2-oleoyl PC (SOPC) > dioleoyl PC (DOPC) > egg yolk PC [8].
  • Our results demonstrate that OxPAPC treatment activated in a time-dependent fashion protein kinase C (PKC), protein kinase A (PKA), Raf/MEK1,2/Erk-1,2 MAP kinase cascade, JNK MAP kinase and transient protein tyrosine phosphorylation in human pulmonary artery endothelial cells (HPAEC), whereas nonoxidized PAPC was without effect [9].

Associations of PCDH8 with chemical compounds

  • OxPAPC, but not nonoxidized PAPC, markedly attenuated the LPS-induced tissue inflammation, barrier disruption, and cytokine production over a range of doses [10].
  • PC species containing palmitoyl- in the sn-1 position and palmitoyl- (DPPC), arachidonyl- (PAPC), linoleoyl- (PLPC) or oleoyl- (POPC) in the sn-2 position were compared [11].
  • Large, unilamellar egg PC, palmitoyloleoyl-PC (POPC), dioleoyl-PC (DOPC), palmitoylarachidonoyl-PC (PAPC), and palmitoyldocosahexaenoyl-PC (P-22:6-PC) vesicles containing no cholesterol or approximately 15 or 30 mol % cholesterol have been examined [12].
  • The enzyme was assayed using vesicles containing arachidonate-containing phospholipid substrate, such as 1-palmitoyl-2-arachidonoylphosphatidylcholine (PAPC) or 1-stearoyl-2-arachidonoylphosphatidylinositol (SAPI), dispersed within vesicles of 1,2-dimyristoylphosphatidylmethanol (DMPM) [13].
  • In order to obtain C-H stretching mode spectra relevant solely to the sn-1 chains of PAPC and PDPC, liquid-phase spectra of arachidonic and docosahexaenoic acid, respectively, were subtracted from the observed phospholipid spectra [14].

Analytical, diagnostic and therapeutic context of PCDH8

  • Biologically active and inactive HPLC fractions of Ox-PAPC were compared by fast atom bombardment-mass spectrometry which revealed that active fractions possessed ions with a mass to charge [correction of change] ratio greater than native PAPC by multiples of 16 D suggesting the addition of 3 and 4 oxygen atoms to PAPC [15].
  • Lineloyl-palmitoyl (PLPC) and arachidonoyl-palmitoyl (PAPC) phosphatidylcholine were oxidized under Fenton reaction conditions (H2O2 and Fe2+), and the short-chain products formed were identified by electrospray ionization mass spectrometry (ESI-MS) [16].
  • Finally, intradermal injections of PAF and PAPC into the ventral ears of rats demonstrated that PAPC was 100x less potent in vivo [17].


  1. Paraxial protocadherin mediates cell sorting and tissue morphogenesis by regulating C-cadherin adhesion activity. Chen, X., Gumbiner, B.M. J. Cell Biol. (2006) [Pubmed]
  2. The molecular species composition of phosphatidylcholine affects cellular properties in normal and sickle erythrocytes. Kuypers, F.A., Chiu, D., Mohandas, N., Roelofsen, B., Op den Kamp, J.A., Lubin, B. Blood (1987) [Pubmed]
  3. Mitogen-activated protein kinase phosphatase 1 activity is necessary for oxidized phospholipids to induce monocyte chemotactic activity in human aortic endothelial cells. Reddy, S., Hama, S., Grijalva, V., Hassan, K., Mottahedeh, R., Hough, G., Wadleigh, D.J., Navab, M., Fogelman, A.M. J. Biol. Chem. (2001) [Pubmed]
  4. Arcadlin is a neural activity-regulated cadherin involved in long term potentiation. Yamagata, K., Andreasson, K.I., Sugiura, H., Maru, E., Dominique, M., Irie, Y., Miki, N., Hayashi, Y., Yoshioka, M., Kaneko, K., Kato, H., Worley, P.F. J. Biol. Chem. (1999) [Pubmed]
  5. Characterization of two novel protocadherins (PCDH8 and PCDH9) localized on human chromosome 13 and mouse chromosome 14. Strehl, S., Glatt, K., Liu, Q.M., Glatt, H., Lalande, M. Genomics (1998) [Pubmed]
  6. Screening the human protocadherin 8 (PCDH8) gene in schizophrenia. Bray, N.J., Kirov, G., Owen, R.J., Jacobsen, N.J., Georgieva, L., Williams, H.J., Norton, N., Spurlock, G., Jones, S., Zammit, S., O'Donovan, M.C., Owen, M.J. Genes Brain Behav. (2002) [Pubmed]
  7. Amino acid residue 149 of lecithin:cholesterol acyltransferase determines phospholipase A2 and transacylase fatty acyl specificity. Wang, J., Gebre, A.K., Anderson, R.A., Parks, J.S. J. Biol. Chem. (1997) [Pubmed]
  8. Lipid headgroup spacing and peptide penetration, but not peptide oligomerization, modulate peptide-induced fusion. Pécheur, E.I., Sainte-Marie, J., Bienvenüe, A., Hoekstra, D. Biochemistry (1999) [Pubmed]
  9. Signal transduction pathways activated in human pulmonary endothelial cells by OxPAPC, a bioactive component of oxidized lipoproteins. Birukov, K.G., Leitinger, N., Bochkov, V.N., Garcia, J.G. Microvasc. Res. (2004) [Pubmed]
  10. Oxidized phospholipids reduce vascular leak and inflammation in rat model of acute lung injury. Nonas, S., Miller, I., Kawkitinarong, K., Chatchavalvanich, S., Gorshkova, I., Bochkov, V.N., Leitinger, N., Natarajan, V., Garcia, J.G., Birukov, K.G. Am. J. Respir. Crit. Care Med. (2006) [Pubmed]
  11. Phospholipid composition of reconstituted high density lipoproteins influences their ability to inhibit endothelial cell adhesion molecule expression. Baker, P.W., Rye, K.A., Gamble, J.R., Vadas, M.A., Barter, P.J. J. Lipid Res. (2000) [Pubmed]
  12. Influence of cholesterol on equilibrium and dynamic bilayer structure of unsaturated acyl chain phosphatidylcholine vesicles as determined from higher order analysis of fluorescence anisotropy decay. Straume, M., Litman, B.J. Biochemistry (1987) [Pubmed]
  13. Cooperativity and binding in the mechanism of cytosolic phospholipase A2. Burke, J.R., Witmer, M.R., Tredup, J., Micanovic, R., Gregor, K.R., Lahiri, J., Tramposch, K.M., Villafranca, J.J. Biochemistry (1995) [Pubmed]
  14. Packing characteristics of highly unsaturated bilayer lipids: Raman spectroscopic studies of multilamellar phosphatidylcholine dispersions. Litman, B.J., Lewis, E.N., Levin, I.W. Biochemistry (1991) [Pubmed]
  15. Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. Watson, A.D., Berliner, J.A., Hama, S.Y., La Du, B.N., Faull, K.F., Fogelman, A.M., Navab, M. J. Clin. Invest. (1995) [Pubmed]
  16. Fragmentation study of short-chain products derived from oxidation of diacylphosphatidylcholines by electrospray tandem mass spectrometry: identification of novel short-chain products. Reis, A., Domingues, P., Ferrer-Correia, A.J., Domingues, M.R. Rapid Commun. Mass Spectrom. (2004) [Pubmed]
  17. Identification and pharmacological characterization of platelet-activating factor and related 1-palmitoyl species in human inflammatory blistering diseases. Travers, J.B., Murphy, R.C., Johnson, C.A., Pei, Y., Morin, S.M., Clay, K.L., Barber, L.A., Hood, A.F., Morelli, J.G., Williams, D.A. Prostaglandins Other Lipid Mediat. (1998) [Pubmed]
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